Early Detection of Critical Pulmonary Shunts in Infants

This paper aims to improve the design of modern Medical Cyber Physical Systems through the addition of supplemental noninvasive monitors. Specifically, we focus on monitoring the arterial blood oxygen content (CaO2), one of the most closely observed vital signs in operating rooms, currently measured by a proxy - peripheral hemoglobin oxygen saturation (SpO2). While SpO2 is a good estimate of O2 content in the finger where it is measured, it is a delayed measure of its content in the arteries. In addition, it does not incorporate system dynamics and is a poor predictor of future CaO2 values. Therefore, as a first step towards supplementing the usage of SpO2, this work introduces a predictive monitor designed to provide early detection of critical drops in CaO2 caused by a pulmonary shunt in infants. To this end, we develop a formal model of the circulation of oxygen and carbon dioxide in the body, characterized by unknown patient-unique parameters. Employing the model, we design a matched subspace detector to provide a near constant false alarm rate invariant to these parameters and modeling uncertainties. Finally, we validate our approach on real-patient data from lung lobectomy surgeries performed at the Children\u27s Hospital of Philadelphia. Given 198 infants, the detector predicted 81% of the critical drops in CaO2 at an average of about 65 seconds earlier than the SpO2-based monitor, while achieving a 0:9% false alarm rate (representing about 2 false alarms per hour)

OpenICE-lite: Towards a Connectivity Platform for the Internet of Medical Things

The Internet of Medical Things (IoMT) is poised to revolutionize medicine. However, medical device communication, coordination, and interoperability present challenges for IoMT applications due to safety, security, and privacy concerns. These challenges can be addressed by developing an open platform for IoMT that can provide guarantees on safety, security and privacy. As a first step, we introduce OpenICE-lite, a middleware for medical device interoperability that also provides security guarantees and allows other IoMT applications to view/analyze the data in real time. We describe two applications that currently utilize OpenICE-lite, namely (i) a critical pulmonary shunt predictor for infants during surgery; (ii) a remote pulmonary monitoring systems (RePulmo). Implementations of both systems are utilized by the Children’s Hospital of Philadelphia (CHOP) as quality improvements to patient care

Aspects of pediatric hemodynamics. A study of young children undergoing corrective heart surgery.

AbstractBackground: Assessing critically ill patients is demanding because their clinical signs are not always easy to interpret. This is particularly true for pediatric patients, due to their small size and robust circulatory compensatorymechanism. Physicians working in pediatric intensive care settings seldom use invasive monitoring, due to possible complications and the risks involved. Instead, they rely on simple vital parameters and blood gases during their clinical work. However, a number of studies have shown that this clinical approach can provide inaccurate data when dealing with critically ill patients. There are very few monitors currently available that have been fully validated for estimating hemodynamic parameters in young children. A less invasive hemodynamic monitor could help physicians make clinical decisions and improve future levels of care, by providing more reliable information on the perioperative hemodynamic status of pediatric patients, without additional risks.Purpose: The primary aim of the studies in this thesis was to look at different aspects of pediatric hemodynamics, by comparing the novel hemodynamic COstatus monitor, with earlier reference methods. In our studies we analyzed: 1) aggrement and precision of cardiac output, 2) detection and estimation of of intracardiac shunts and 3) estimation of different blood volumes. A secondary aim of this thesis was to establish reference values of hemodynamic values in young children using COstatus, and comparing idexing of same values with body surface area and body weight.Methods: Children (under 15 kilograms) undergoing corrective heart surgery at Lund Children´s Hospital were enrolled in our studies.Results:Paper I – Estimation of cardiac outputThe COstatus provided excellent precision and agreement in estimating cardiac output in young children, compared with perivascular flow probe placed around the ascending aorta.Paper II – Estimation of intracardiac shunts. The COstatus detected intracardiac shunts to the same extent as the “gold standard” echocardiography. However, it slightly underestimated the degrees of the shunts in small and moderate shunts when it was compared to two other reference methods, namely perivascular ultrasonic flow probes (placed around the pulmonary truncus and ascending aorta) and the oximetric shunt equation (using arterial and venous blood gases).Paper III – Normalization of hemodynamic parameters. Body weight produced a better normalization of hemodynamic parameters than body surface area in young children.Paper IV – Estimation of oxygen uptake. Indirect calorimetry seemed to overestimate oxygen uptake in youngchildren, compared to the reverse Fick method.Paper V – Estimation of body surface area. Commonly used body surface area formulas disagreed in youngchildren, Mosteller formula came closest to the mean body surface area.Conclusions: COstatus is accurate, precise and less invasive than earlier reference methods and might enable future cardiac output comparison studies in the intensive care setting. COstatus detects shunts accurately but algorithms for shunt size estimations might be overly cautious. Caution is advised regarding the use of indirect calorimetry and direct Fick method in cardiac output comparison studies

Parameter-Invariant Design of Medical Alarms

The recent explosion of low-power low-cost communication, sensing, and actuation technologies has ignited the automation of medical diagnostics and care in the form of medical cyber physical systems (MCPS). MCPS are poised to revolutionize patient care by providing smarter alarm systems, clinical decision support, advanced diagnostics, minimally invasive surgical care, improved patient drug delivery, and safety and performance guarantees. With the MCPS revolution emerges a new era in medical alarm systems, where measurements gathered via multiple devices are fused to provide early detection of critical conditions. The alarms generated by these next generation monitors can be exploited by MCPS to further improve performance, reliability, and safety. Currently, there exist several approaches to designing medical monitors ranging from simple sensor thresholding techniques to more complex machine learning approaches. While all the current design approaches have different strengths and weaknesses, their performance degrades when underlying models contain unknown parameters and training data is scarce. Under this scenario, an alternative approach that performs well is the parameter-invariant detector, which utilizes sufficient statistics that are invariant to unknown parameters to achieve a constant false alarm rate across different systems. Parameter-invariant detectors have been successfully applied in other cyber physical systems (CPS) applications with structured dynamics and unknown parameters such as networked systems, smart buildings, and smart grids; most recently, the parameter-invariant approach has been recently extended to medical alarms in the form of a critical shunt detector for infants undergoing a lung lobectomy. The clinical success of this case study application of the parameter-invariant approach is paving the way for a range of other medical monitors. In this tutorial, we present a design methodology for medical parameter-invariant monitors. We begin by providing a motivational review of currently employed medical alarm techniques, followed by the introduction of the parameter-invariant design approach. Finally, we present a case study example to demonstrate the design of a parameter-invariant alarm for critical shunt detection in infants during surgical procedures

Management of late presentation congenital heart disease

In many parts of the world, mostly low- and middle-income countries, timely diagnosis and repair of congenital heart diseases (CHDs) is not feasible for a variety of reasons. In these regions, economic growth has enabled the development of cardiac units that manage patients with CHD presenting later than would be ideal, often after the window for early stabilisation - transposition of the great arteries, coarctation of the aorta - or for lower-risk surgery in infancy - left-to-right shunts or cyanotic conditions. As a result, patients may have suffered organ dysfunction, manifest signs of pulmonary vascular disease, or the sequelae of profound cyanosis and polycythaemia. Late presentation poses unique clinical and ethical challenges in decision making regarding operability or surgical candidacy, surgical strategy, and perioperative intensive care management

Context-Aware Detection in Medical Cyber-Physical Systems

This paper considers the problem of incorporating context in medical cyber-physical systems (MCPS) applications for the purpose of improving the performance of MCPS detectors. In particular, in many applications additional data could be used to conclude that actual measurements might be noisy or wrong (e.g., machine settings might indicate that the machine is improperly attached to the patient); we call such data context. The first contribution of this work is the formal definition of context, namely additional information whose presence is associated with a change in the measurement model (e.g., higher variance). Given this formulation, we developed the context-aware parameter-invariant (CA-PAIN) detector; the CA-PAIN detector improves upon the original PAIN detector by recognizing events with noisy measurements and not raising unnecessary false alarms. We evaluate the CA-PAIN detector both in simulation and on real-patient data; in both cases, the CA-PAIN detector achieves roughly a 20-percent reduction of false alarm rates over the PAIN detector, thus indicating that formalizing context and using it in a rigorous way is a promising direction for future work

Intravascular ultrasound and magnetic resonance imaging of the pulmonary arteries in pulmonary hypertension

Two relatively new techniques by which the pulmonary arteries can be imaged in life are intravascular ultrasound and magnetic resonance imaging. The main aim of this thesis is to describe the changes which are detectable on intravascular ultrasound and magnetic resonance imaging in patients with pulmonary hypertension and to determine whether these imaging modalities could be of use for the clinical assessment of the condition.Intravascular ultrasound was performed in 10 young adults with Eisenmenger's Syndrome and 4 infants with pulmonary hypertension secondary to a left to right shunt. Vasodilator studies were performed in 5 of the patients with Eisenmenger's. The vessel wall appeared as a single echogenic layer in all patients, making it difficult to define or measure medial thickness with certainty. Morphological changes of intimal hypertrophy and atherosclerosis were evident in patients with Eisenmenger's whereas in the infants the intima appeared thin and smooth, typical of normal artery. The technique gave excellent definition of the vessel lumen allowing continuous measurement of changes in luminal dimensions in response to vasodilators.MRI of the pulmonary arteries was performed in 11 patients with Eisenmenger's and 6 normal controls. In patients with pulmonary hypertension the pulmonary arteries were found to be dilated with reduced distensibility 4 when compared with normals. Calculations of Qp:Qs by MRI in patients with systemic to pulmonary shunts and pulmonary hypertension did not correlate well with values from cardiac catheterisation in all patients.As intravascular and magnetic resonance imaging are confined to the elastic pulmonary arteries, quantitative morphological studies were peformed on 24 post mortem specimens of lungs from patients who had died with pulmonary hypertension to determine whether there was any correlation between changes in the elastic pulmonary arteries and severity of pulmonary vascular disease. When compared with normals there was medial thickening in those with pulmonary hypertension but this was of an insufficient degree to be detectable by current ultrasound catheters. There was no correlation between degree of medial thickening in the elastic pulmonary arteries and severity of pulmonary vascular disease but intimal thickening and atherosclerosis were evident in those with more advanced disease.In conclusion, magnetic resonance imaging was found to have limited role in the assesssment of pulmonary hypertension but with new technical developments could become a non-invasive method of studying pulmonary hypertension in the future. The morphological changes detectable by intravascular ultrasound tend to be in severe disease only but the technique provides a unique method of studying pulmonary vascular reactivity in life

Track 2: Catheter interventions from fetus to adult

Catheter interventions from fetus to adult

Quantification of left-to-right shunt through Patent Ductus Arteriosus by colour Doppler

The aim of this thesis was to develop a non-invasive method to quantify the size of a shunt through a patent ductus arteriosus (PDA) by ultrasound and to test its usability in clinical settings. There is no consensus regarding the optimal management strategy for a PDA in premature infants. Non-steroidal anti-inflammatory drugs (NSAID) are the first treatment of choice. The use of NSAIDs, especially indomethacin, should be carefully balanced, as they have their disadvantages. In our experimental study in lambs, indomethacin acutely reduced the coronary flow by up to 50% and the effect lasted for up to one hour. In our lamb model, we developed a non-invasive method to quantify the ductal shunt by ultrasound. The flow was measured with electromagnetic flow meters in the ascending aorta and in the ductus and a colour Doppler image was obtained simultaneously over the main pulmonary artery longitudinal cross-section including ductal inflow. The percentage of colour pixels representing ductal flow was quantified in the main pulmonary artery outlined by anatomic landmarks. There was a correlation between the ratio of pulmonary to systemic flow (Qp/Qs) and the percentage of total colours covering the cross-section and there was an even better correlation with green pixels alone. When the Qp/Qs was ≥ 1.5:1, the percentage of green pixels in PALS was ≥ 50. In children admitted for the device closure of the open ductus, the method had 92% sensitivity for a measured Qp/Qs of ≥ 1.5. In preterm infants during the first three days of life, the ductal diameter but not the quantified ductal shunt predicted the need for treatment. We showed further that the perinatal cytokine burden during the first three days of life is not associated with an increased need to close the ductus, but it is associated with increased ductal diameter and reduced systolic blood pressure. We suggest that our method could be used as a non-invasive tool to determine a haemodynamically significant ductal shunt. Using the evaluated Qp/Qs of > 1.5:1 as a guide for treatment decisions might reduce the need for unnecessary interventions and reduce complications