Computational methods for physiological data

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2009.Author is also affiliated with the MIT Dept. of Electrical Engineering and Computer Science. Cataloged from PDF version of thesis.Includes bibliographical references (p. 177-188).Large volumes of continuous waveform data are now collected in hospitals. These datasets provide an opportunity to advance medical care, by capturing rare or subtle phenomena associated with specific medical conditions, and by providing fresh insights into disease dynamics over long time scales. We describe how progress in medicine can be accelerated through the use of sophisticated computational methods for the structured analysis of large multi-patient, multi-signal datasets. We propose two new approaches, morphologic variability (MV) and physiological symbolic analysis, for the analysis of continuous long-term signals. MV studies subtle micro-level variations in the shape of physiological signals over long periods. These variations, which are often widely considered to be noise, can contain important information about the state of the underlying system. Symbolic analysis studies the macro-level information in signals by abstracting them into symbolic sequences. Converting continuous waveforms into symbolic sequences facilitates the development of efficient algorithms to discover high risk patterns and patients who are outliers in a population. We apply our methods to the clinical challenge of identifying patients at high risk of cardiovascular mortality (almost 30% of all deaths worldwide each year). When evaluated on ECG data from over 4,500 patients, high MV was strongly associated with both cardiovascular death and sudden cardiac death. MV was a better predictor of these events than other ECG-based metrics. Furthermore, these results were independent of information in echocardiography, clinical characteristics, and biomarkers.(cont.) Our symbolic analysis techniques also identified groups of patients exhibiting a varying risk of adverse outcomes. One group, with a particular set of symbolic characteristics, showed a 23 fold increased risk of death in the months following a mild heart attack, while another exhibited a 5 fold increased risk of future heart attacks.by Zeeshan Hassan Syed.Ph.D

Strategies for Untargeted Biomarker Discovery in Biological Fluids

The health status of an organism modulates the dynamic and complex interplay of biochemical species that make-up the body and fluids of the organism. As such, these biological fluids are routinely used for diagnostic testing, yet they are often not used to their full potential. For instance, amniotic fluid (AF), the fluid that surrounds the fetus during gestation, is collected primarily for genetic testing from women with identified risk factors. The AF proteome and/or metabolome are seldom considered and represent a largely untapped wealth of relevant clinical information. Extensive, multi-analyte data can be collected from biological samples with modern analytical instrumentation. However, sophisticated data preprocessing and analysis (i.e. chemometrics) are required to reveal the relationships between the biochemical signals and the health status. This thesis seeks to demonstrate that untargeted biomarker discovery strategies can be efficiently applied to the task of finding novel biomarkers and complement the traditional hypothesis driven approaches. In the work underlying this thesis, a chemometric data analysis strategy was developed to search for biomarkers in capillary electrophoresis (CE) separations data. The absorbance data from amniotic fluid samples (n=107) collected at 15 weeks gestation, at 195 +/- 4 nm, was normalized, time aligned with Correlation Optimized Warping and reduced to a smaller number of variables by Haar transformation. The reduced data was then classified into normal or abnormal health classes by using a Bayes classifier algorithm. The chemometric data analysis was first employed to find biomarkers of gestational diabetes mellitus (GDM) and revealed that human serum albumin (HSA) could predict the early onset of disease. The same approach was successfully used to identify cases of large-for-gestational age (LGA) with the same AF CE-UV data. It was also employed for the classification of embryos with high and low reproductive potential using in vitro fertilization (IVF) culture media analyzed by CE-UV. Overall, a chemometric method was developed to perform untargeted biomarker discovery in biological samples and provide new means to detect GDM pregnancies, LGA neonates and viable embryos in IVF. The method was successful at identifying biomarkers of interest and showed high flexibility and transferability to other biological fluids

Cortical Autonomic Alterations with Hypertension

Objective: This study tested whether the medial prefrontal cortex (MPFC) is differentially involved in human cardiovagal control in normotensive (NT) versus hypertensive (HT) subjects. Design: Functional magnetic resonance imaging was combined with measures of heart rate (HR) and baroreflex sensitivity (BRS) during a 30-sec static handgrip (HG; 30% maximal strength) task. Results: Baseline HR was higher in HT (68±3 bpm) versus NT (59±2 bpm). Cardiovagal baroreflex sensitivity was lower in HT (6.8±1.7 msec/mniHg) versus NT (16.4±2.2 msec/mmHg). During HG, HR increased similarly in HT (2±1 bpm) and NT (4±1 bpm). In NT, the HR response was associated with deactivation in the MPFC. MPFC activity did not change in HT. In 11 of the total 23 subjects, HR increased \u3e 3 bpm and MPFC deactivation was correlated with the HR time course. Conclusions: Overall, hypertension appears to be equivalent to normotension in terms of the HR response to HG and the MPFC-HR associatio

Acoustic sensing as a novel approach for cardiovascular monitoring at the wrist

Cardiovascular diseases are the number one cause of deaths globally. An increased cardiovascular risk can be detected by a regular monitoring of the vital signs including the heart rate, the heart rate variability (HRV) and the blood pressure. For a user to undergo continuous vital sign monitoring, wearable systems prove to be very useful as the device can be integrated into the user's lifestyle without affecting the daily activities. However, the main challenge associated with the monitoring of these cardiovascular parameters is the requirement of different sensing mechanisms at different measurement sites. There is not a single wearable device that can provide sufficient physiological information to track the vital signs from a single site on the body. This thesis proposes a novel concept of using acoustic sensing over the radial artery to extract cardiac parameters for vital sign monitoring. A wearable system consisting of a microphone is designed to allow the detection of the heart sounds together with the pulse wave, an attribute not possible with existing wrist-based sensing methods. Methods: The acoustic signals recorded from the radial artery are a continuous reflection of the instantaneous cardiac activity. These signals are studied and characterised using different algorithms to extract cardiovascular parameters. The validity of the proposed principle is firstly demonstrated using a novel algorithm to extract the heart rate from these signals. The algorithm utilises 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. The HRV in the short-term acoustic recordings is found by extracting the S1 events using the relative information between the short- and long-term energies of the signal. The S1 events are localised using three different characteristic points and the best representation is found by comparing the instantaneous heart rate profiles. The possibility of measuring the blood pressure using the wearable device is shown by recording the acoustic signal under the influence of external pressure applied on the arterial branch. The temporal and spectral characteristics of the acoustic signal are utilised to extract the feature signals and obtain a relationship with the systolic blood pressure (SBP) and diastolic blood pressure (DBP) respectively. Results: This thesis proposes three different algorithms to find the heart rate, the HRV and the SBP/ DBP readings from the acoustic signals recorded at the wrist. The results obtained by each algorithm are as follows: 1. The heart rate algorithm is 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. A high statistical agreement between the heart rate obtained from the acoustic signal and the photoplethysmography (PPG) signal is observed. 2. The HRV algorithm is validated on the short-term acoustic signals of 5-minutes duration recorded from each of the 12 subjects. A comparison is established with the simultaneously recorded electrocardiography (ECG) and PPG signals respectively. The instantaneous heart rate for all the subjects combined together achieves an accuracy of 98.50% and 98.96% with respect to the ECG and PPG signals respectively. The results for the time-domain and frequency-domain HRV parameters also demonstrate high statistical agreement with the ECG and PPG signals respectively. 3. The algorithm proposed for the SBP/ DBP determination is validated on 104 acoustic signals recorded from 40 adult subjects. The experimental outputs when compared with the reference arm- and wrist-based monitors produce a mean error of less than 2 mmHg and a standard deviation of error around 6 mmHg. Based on these results, this thesis shows the potential of this new sensing modality to be used as an alternative, or to complement existing methods, for the continuous monitoring of heart rate and HRV, and spot measurement of the blood pressure at the wrist.Open Acces

Analysis of Ventricular Depolarisation and Repolarisation Using Registration and Machine Learning

Our understanding of cardiac diseases has greatly advanced since the advent of electrocardiography (ECG). With the increasing influx of available data in recent times, significant research efforts have been put forth to automate the study and detection of cardiac conditions. Naturally, the focus has progressed toward studying dynamic changes in ventricular depolarisation and repolarisation across serial recordings - as complex beat-to-beat changes in morphology manifest over time. Manual extraction of diagnostic and prognostic markers is a laborious task. Hence, automated and accurate methods are required to extract markers for the study of ventricular lability and detection of common diseases, such as myocardial ischemia and myocardial infarction. The aim of this thesis is to improve automated marker extraction and detection of diseases for the study of ventricular depolarisation and repolarisation lability in ECG. As such, two novel template adaptation methods capable of capturing complex beat-to-beat morphological changes are proposed for three-dimensional and two-dimensional data, respectively. The proposed three-dimensional template adaptation method provides an inhomogeneous method for transforming template vectorcardiogram (VCG) by exploiting registrationinspired parametrisation and an efficient kernel ridge regression formulation. Analysis across simulated data and clinical myocardial infarction data demonstrates state-of-the-art results. The two-dimensional template adaptation method draws from traditional registrationbased techniques and treats the ECG as a two-dimensional point set problem. Validation against previously employed simulated data and a gold-standard annotated clinical database demonstrate the highest level of performance. Subsequently, frameworks employing the proposed template adaptation techniques are developed for the automated detection of ischemic beats and myocardial infarction. Furthermore, a small study analysing ventricular repolarisation variability (VRV) in non-ischemic cardiomyopathy (CM) is considered, utilising markers of cardiac lability proposed in the development of the three-dimensional template adaptation system. In summary, this thesis highlights the necessity for custom template adaptation methods for the accurate measurement of beat-to-beat variability in cardiac data. Two novel stateof- the-art methods are proposed and extended to study myocardial ischemia, myocardial infarction and non-ischemic CM.Thesis (Ph.D.) -- University of Adelaide, School of Electrical and Electronic Engineering, 202

Anthropometric and genetic determinants of cardiac morphology and function

Background Cardiac structure and function result from complex interactions between genetic and environmental factors. Population-based studies have relied on 2-dimensional cardiovascular magnetic resonance as the gold-standard for phenotyping. However, this technique provides limited global metrics and is insensitive to regional or asymmetric changes in left ventricular (LV) morphology. High-resolution 3-dimensional cardiac magnetic resonance (3D-CMR) with computational quantitative phenotyping, might improve on traditional CMR by enabling the creation of detailed 3D statistical models of the variation in cardiac phenotypes for use in studies of genetic and/or environmental effects on cardiac form or function. Purpose To determine whether 3D-CMR is applicable at scale, and provides methodological and statistical advantages over conventional imaging for large-scale population studies and to apply 3D-CMR to anthropometric and genetic studies of the heart. Methods 1530 volunteers (54.8% females, 74.7% Caucasian, mean age 41.3±13.0 years) without self-reported cardiovascular disease were recruited prospectively to the Digital Heart Project. Using a cardiac atlas-based software, these images were computationally processed and quantitatively analysed. Parameters such as myocardial shape, curvature, wall thickness, relative wall thickness, end-systolic wall stress, fractional wall thickening and ventricular volumes were extracted at over 46,000 points in the model. The relationships between these parameters and systolic blood pressure (SBP), fat mass, lean mass and genetic variationswere analysed using 3D regression models adjusted for body surface area, gender, race, age and multiple testing. Targeted resequencing of titin (TTN), the largest human gene and the commonest genetic cause of dilated cardiomyopathy, was performed in 928 subjects while common variants (~700.000) were genotyped in 1346 subjects. Results Automatically segmented 3D images were more accurate than 2D images at defining cardiac surfaces, resulting in fewer subjects being required to detect a statistically significant 1 mm difference in wall thickness. 3D-CMR enabled the detection of a strong and distinct regionality of the effects of SBP, body composition and genetic variation on the heart. It shows that the precursors of the hypertensive heart phenotype can be traced to healthy normotensives and that different ratios of body composition are associated with particular gender-specific patterns of cardiac remodelling. In 17 asymptomatic subjects with genetic variations associated with dilated cardiomyopathy, early stages of ventricular impairment and wall thinning were identified, which were not apparent by 2D imaging. Conclusions 3D-CMR combined with computational modelling provides high-resolution insight into the earliest stages of heart disease. These methods show promise for population-based studies of the anthropometric, environmental and genetic determinants of LV form and function in health and disease.Open Acces

Intelligent Biosignal Processing in Wearable and Implantable Sensors

This reprint provides a collection of papers illustrating the state-of-the-art of smart processing of data coming from wearable, implantable or portable sensors. Each paper presents the design, databases used, methodological background, obtained results, and their interpretation for biomedical applications. Revealing examples are brain–machine interfaces for medical rehabilitation, the evaluation of sympathetic nerve activity, a novel automated diagnostic tool based on ECG data to diagnose COVID-19, machine learning-based hypertension risk assessment by means of photoplethysmography and electrocardiography signals, Parkinsonian gait assessment using machine learning tools, thorough analysis of compressive sensing of ECG signals, development of a nanotechnology application for decoding vagus-nerve activity, detection of liver dysfunction using a wearable electronic nose system, prosthetic hand control using surface electromyography, epileptic seizure detection using a CNN, and premature ventricular contraction detection using deep metric learning. Thus, this reprint presents significant clinical applications as well as valuable new research issues, providing current illustrations of this new field of research by addressing the promises, challenges, and hurdles associated with the synergy of biosignal processing and AI through 16 different pertinent studies. Covering a wide range of research and application areas, this book is an excellent resource for researchers, physicians, academics, and PhD or master students working on (bio)signal and image processing, AI, biomaterials, biomechanics, and biotechnology with applications in medicine

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 377)

This bibliography lists 223 reports, articles, and other documents recently introduced into the NASA Scientific and Technical Information System. Subject coverage includes: aerospace medicine and physiology, life support systems and man/system technology, protective clothing, exobiology and extraterrestrial life, planetary biology, and flight crew behavior and performance

Non-Invasive Imaging for the Assessment of Cardiac Dose and Function Following Focused External Beam Irradiation

Technological advances in imaging and radiotherapy have led to significant improvement in the survival rate of breast cancer patients. However, a larger proportion of patients are now exhibiting the less understood, latent effects of incidental cardiac irradiation that occurs during left-sided breast radiotherapy. Here, we examine the utility of four-dimensional computed tomography (4D-CT) for the accurate assessment of cardiac dose; and a hybrid positron emission tomography (PET) magnetic resonance imaging (MRI) system to longitudinally study radiation-induced cardiac effects in a canine model. Using 4D-CT and deformable dose accumulation, we assessed the variation caused by breathing motion in the estimated dose to the heart, left-ventricle, and left anterior descending artery (LAD) of left-sided breast cancer patients. The LAD showed substantial variation in dose due to breathing. In light of this, we suggest the use of 4D-CT and dose accumulation for future clinical studies looking at the relationship between LAD dose and cardiac toxicity. Although symptoms of cardiac dysfunction may not manifest clinically for 10-15 years post radiation, PET-MRI can potentially identify earlier changes in cardiac inflammation and perfusion that are typically asymptomatic. Using PET-MRI, the progression of radiation-induced cardiac toxicity was assessed in a large animal model. Five canines were imaged using 13N-ammonia and 18F-fluorodeoxyglucose (FDG) PET-MRI to assess changes in myocardial perfusion and inflammation, respectively. All subjects were imaged at baseline, 1 week, 4 weeks, 3 months, 6 months, and 12 months after focused cardiac irradiation. To the best of our knowledge PET has not been previously used to assess cardiac perfusion following irradiation. The delivered dose to the heart, left ventricle, LAD, and left circumflex artery were comparable to what has been observed during breast radiotherapy. Relative to baseline, a transient increase in myocardial perfusion was observed followed by a gradual return to baseline. However, a persistent increase in FDG uptake was observed throughout the entire left ventricle, including both irradiated and less-irradiated portions of the heart. In light of these findings, we suggest the use of this imaging approach for future human studies to assess mitigation strategies aimed at minimizing cardiac exposure and long-term toxicity subsequent to left-sided breast irradiation

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 243)

This bibliography lists 282 reports, articles and other documents introduced into the NASA scientific and technical information system in February 1983