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)

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

Accuracy of prospective two-dimensional/Doppler echocardiography in the assessment of reparative surgery

Between January 1987 and January 1989, all 129 patients (aged 11 days to 25 years, median 39 months) undergoing both an echocardiographic examination and cardiac catheterization after reparative surgery were prospectively included in a study to assess the accuracy of combined two-dimensional and Doppler color flow imaging. The patient diagnoses were transposition of the great arteries (n = 20), tetralogy of Fallot (n = 38), coarctation of the aorta (n = 24), complete atrioventricular (AV) canal (n = 15), atrial septal defect (n = 8), ventricular septal defects (n = 3), pulmonary stenosis (n = 4), aortic stenosis (n = 8) and subaortic stenosis (n = 9).In arterial tract stenosis, there was high correlation between Doppler estimates and catheterization-derived measurements of residual right ventricular outflow tract obstruction in patients after the arterial switch operation for transposition of the great arteries (r = 0.95) as well as in patients after corrective repair of tetralogy of Fallot (r = 0.84).In semilunar/AV valve regurgitation, graded as none, mild, moderate or severe, echocardiographic estimates correlated exactly with angiographic grading in 84% and differed by one angiographic grade in the other 16%.In residual left to right shunting, no hemodynamically significant shunt was missed by echocardiography. For residual shunts at the ventricular level (n = 32), addition of Doppler color flow imaging improved the sensitivity (from 63% to 94%) and the negative predictive value (from 88% to 98%).In elevated right ventricular pressure, Doppler-derived right ventricular-right atrial pressure estimates in 24 patients correlated well with catheterization measurements (r = 0.93).Combined two-dimensional and Doppler color flow echocardiography was highly accurate in the prospective evaluation of these four types of postoperative residua

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

Parameter-Invariant Monitor Design for Cyber Physical Systems

The tight interaction between information technology and the physical world inherent in Cyber-Physical Systems (CPS) can challenge traditional approaches for monitoring safety and security. Data collected for robust CPS monitoring is often sparse and may lack rich training data describing critical events/attacks. Moreover, CPS often operate in diverse environments that can have significant inter/intra-system variability. Furthermore, CPS monitors that are not robust to data sparsity and inter/intra-system variability may result in inconsistent performance and may not be trusted for monitoring safety and security. Towards overcoming these challenges, this paper presents recent work on the design of parameter-invariant (PAIN) monitors for CPS. PAIN monitors are designed such that unknown events and system variability minimally affect the monitor performance. This work describes how PAIN designs can achieve a constant false alarm rate (CFAR) in the presence of data sparsity and intra/inter system variance in real-world CPS. To demonstrate the design of PAIN monitors for safety monitoring in CPS with different types of dynamics, we consider systems with networked dynamics, linear-time invariant dynamics, and hybrid dynamics that are discussed through case studies for building actuator fault detection, meal detection in type I diabetes, and detecting hypoxia caused by pulmonary shunts in infants. In all applications, the PAIN monitor is shown to have (significantly) less variance in monitoring performance and (often) outperforms other competing approaches in the literature. Finally, an initial application of PAIN monitoring for CPS security is presented along with challenges and research directions for future security monitoring deployments

Pulmonary Artery Acceleration Time Provides a Reliable Estimate of Invasive Pulmonary Hemodynamics in Children

Background Pulmonary artery acceleration time (PAAT) is a non-invasive method to assess pulmonary hemodynamics, but lacks validity in children. This study sought to evaluate the accuracy of Doppler echocardiography (DE) derived PAAT in predicting right heart catheterization (RHC) derived pulmonary arterial pressure (PAP), pulmonary vascular resistance (PVR) and compliance in children. Methods Prospectively acquired and retrospectively measured DE derived PAAT and RHC derived systolic PAP (sPAP), mean PAP (mPAP), index PVR (PVRi) and compliance were compared by regression analysis in a derivation cohort of 75 children (median age, 5.3 years; 1.3–12.6) with wide ranges of pulmonary hemodynamics. To account for heart rate variability, PAAT was adjusted for right ventricle ejection time (RVET) and corrected by the RR interval. Regression equations incorporating PAAT and PAAT:RVET from the derivation cohort were then evaluated for the accuracy of its predictive values for invasive pulmonary hemodynamics in a validation cohort of 50 age- and weight- matched children with elevated PAP and PVR. Results There were significant inverse correlations between PAAT and RHC derived mPAP (r = −0.82) and PVRi (r= −0.78) and direct correlation (r= 0.78) between PAAT and pulmonary compliance in the derivation cohort. For detection of pulmonary hypertension (PRVi > 3 WU x m2 and mPAP > 25 mmHg), PAAT < 90 msec and PAAT:RVET < 0.31 resulted in a sensitivity of 97% and a specificity of 95%. In the derivation cohort, the regression equations relating PAAT with mPAP and PVRi were: mPAP = 48 – 0.28 x PAAT and PVRi = 9 –0.07 x PAAT. These PAAT integrated equations predicted RHC measured pulmonary hemodynamics in the validation cohort with good correlations (r = 0.88, 0.83 respectively), small biases (<10%), and minimal coefficient of variation (<8%). Conclusions PAAT inversely correlates with RHC measured pulmonary hemodynamics and directly correlates with pulmonary arterial compliance in children. The study established PAAT based regression equations in children to accurately predict RHC derived PAP and PVR

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