Multimodal Signal Processing for Diagnosis of Cardiorespiratory Disorders

This thesis addresses the use of multimodal signal processing to develop algorithms for the automated processing of two cardiorespiratory disorders. The aim of the first application of this thesis was to reduce false alarm rate in an intensive care unit. The goal was to detect five critical arrhythmias using processing of multimodal signals including photoplethysmography, arterial blood pressure, Lead II and augmented right arm electrocardiogram (ECG). A hierarchical approach was used to process the signals as well as a custom signal processing technique for each arrhythmia type. Sleep disorders are a prevalent health issue, currently costly and inconvenient to diagnose, as they normally require an overnight hospital stay by the patient. In the second application of this project, we designed automated signal processing algorithms for the diagnosis of sleep apnoea with a main focus on the ECG signal processing. We estimated the ECG-derived respiratory (EDR) signal using different methods: QRS-complex area, principal component analysis (PCA) and kernel PCA. We proposed two algorithms (segmented PCA and approximated PCA) for EDR estimation to enable applying the PCA method to overnight recordings and rectify the computational issues and memory requirement. We compared the EDR information against the chest respiratory effort signals. The performance was evaluated using three automated machine learning algorithms of linear discriminant analysis (LDA), extreme learning machine (ELM) and support vector machine (SVM) on two databases: the MIT PhysioNet database and the St. Vincent’s database. The results showed that the QRS area method for EDR estimation combined with the LDA classifier was the highest performing method and the EDR signals contain respiratory information useful for discriminating sleep apnoea. As a final step, heart rate variability (HRV) and cardiopulmonary coupling (CPC) features were extracted and combined with the EDR features and temporal optimisation techniques were applied. The cross-validation results of the minute-by-minute apnoea classification achieved an accuracy of 89%, a sensitivity of 90%, a specificity of 88%, and an AUC of 0.95 which is comparable to the best results reported in the literature

Craniofacial morphology in subjects with obstructive sleep apnea

Opstruktivna apneja u spavanju (OSA) povezana je s prekomjernom pospanošću tijekom dana ili s barem dvama od sljedećih simptoma: iznenadnim buđenjem s osjećajem gušenja, nedovoljno osvježavajućim spavanjem, umorom tijekom dana i problemima u kognitivnoj sferi. Ponavljajuća okluzija gornjeg dišnog puta tijekom spavanja povezana je s povećanim morbiditetom i mortalitetom od kardiovaskularnih komplikacija. Trenutačno ne postoje informacije o kraniofacijalnim obilježjima osoba s opstruktivnom apnejom u spavanju u Hrvatskoj. Istraživanje je imalo za cilj antropometrijskom i rentgenkefalometrijskom analizom utvrditi kraniofacijalna obilježja pacijenata s opstruktivnom apnejom u spavanju i njihovu povezanost s apnea hipopneja indeksom (AHI). Kod 20 muških ispitanika s OSA i 20 kontrolnih muških ispitanika uzete su antropometrijske mjere i analizirano je 25 varijabli na laterolateralnom rentgenkefalogramu. OSA je definirana kad je AHI 5/h. U usporedbi OSA i kontrolnih ispitanika uočena je statistički značajno povišena srednja vrijednost indeksa tjelesne mase (ITM), opsega vrata (OV) i indeksa glave (IG), a smanjena srednja vrijednost indeksa lica (IL) kod ispitanika s OSA (p <0,01). Ispitanici s OSA su pokazali statistički značajne razlike u rentgenkefalometrijskim varijablama prema kontrolnim ispitanicima: smanjenu duljinu mandibularne ravnine (MP, p<0,05) i prednje kranijalne baze (SN, p <0,01), povećanu udaljenost jezične kosti od mandibularne ravnine (MPH, p<0,05), povećanu duljinu mekog nepca (PNSP, p <0,01), smanjenu širinu gornjeg dišnog puta na dvije razine: velofarinksu (Up-ppw, P-ppw, p <0,01) i orofarinksu (Tbp-ppw, p<0,05; PAS, p<0,01), smanjenu udaljenost jezične kosti od stražnjeg zida farinksa (H-ppw, p<0,01), povećanu kraniocervikalnu angulaciju (OPT-NSL, p <0,01; CTV-NLS, p<0,05), povećan kut između točaka supramentale, menton i jezične kosti (B-Me-H, p<0,05) i povećan kut između točaka spina nasalis posterior, supramentale i jezične kosti (PNS-B-H, p<0,05). Multivarijatna analiza je pokazala vrlo dobru, ali ne i statistički značajnu korelaciju između antropometrijskih prediktorskih varijabli (BMI, IG) i AHI te dobru, ali ne i statistički značajnu korelaciju između rengenkefalometrijskih prediktorskih varijabli (H-ppw, SN i OPT-NSL) i AHI. Ovo istraživanje je pokazalo da između ispitanika s OSA i kontrolnih ispitanika postoje razlike u kraniofacijalnim obilježjima. Rezultati ovog istraživanja ukazuju na potrebu uključivanja specijalista ortodonta u multidisciplinarni tim koji se bavi liječenjem pacijenata s OSA.Introduction: Obstructive Sleep Apnea (OSA) is associated with the excessive drowsiness during the day or with at least two of the following symptoms: sudden awakening with a sensation of suffocation, insufficiently refreshing sleep, tiredness during the day and problems in the cognitive sphere. Repetitive occlusion of the upper airway during sleep is correlated with the increased rates of morbidity and mortality due to cardiovascular complications. Objectives: Currently, there is no data available regarding craniofacial morphology in subjects with obstructive sleep apnea (OSA) in Croatia. The aim of the study was to determine the craniofacial characteristics of subjects with OSA and to assess the correlation of anthropometric and cephalometric variables related to craniofacial morphology with the Apnea Hypopnea Index (AHI). Materials and methods: Anthropometric measurements and upright lateral cephalometric radiographs were obtained from 20 male subjects with OSA and 20 male controls. Twenty five variables were identified and calculated for each cephalometric radiograph. OSA was defined as AHI 5/hour. Results: The OSA subjects showed significantly higher body mass index (BMI), larger neck circumference (NC) and cranial index (CI) and lower facial index (FI) in comparison with the controls (p<0,01). The subjects with OSA showed significant cephalometric features as opposed to the controls: smaller linear distance between gonion and menton (MP, p<0,05) and anterior cranial base (SN, p<0,01), greater linear distance from the hyoid bone to the mandibular plane (MPH, p<0,05), and from the posterior nasal spine to the tip of the soft palate (PNSP, p<0,01). Furthermore, they showed reduced upper airway width at two levels: the velopharynx (Up-ppw, P-ppw, p<0,01), and the oropharings (Tbp-ppw, p<0,05; PAS, p<0,01) and smaller linear distance from the hyoid bone to the posterior wall of the pharynx (H-ppw, p<0,01). They also displayed significantly increased craniocervical angulation (OPT-NSL, p<0,01; CTV-NLS, p<0,05), larger angle between supramentale, menton and hyoid bone (B-Me-H, p<0,05) and larger angle between posterior nasal spine, supramentale and hyoid bone (PNS-B-H, p<0,05). Multivariate analysis showed a very good, but not statistically significant correlation between anthropometric predictor variables (BMI, CI) and AHI, and good, but not statistically significant correlation between cephalometric predictor variables (H-ppw, SN and OPT-NSL) and AHI. Conclusions: This study has proved that OSA subjects and controls have different craniofacial morphology. The results of this study suggest the need to include a specialist orthodontist in the multidisciplinary team dealing with the treatment of OSA patients

Craniofacial morphology in subjects with obstructive sleep apnea

Opstruktivna apneja u spavanju (OSA) povezana je s prekomjernom pospanošću tijekom dana ili s barem dvama od sljedećih simptoma: iznenadnim buđenjem s osjećajem gušenja, nedovoljno osvježavajućim spavanjem, umorom tijekom dana i problemima u kognitivnoj sferi. Ponavljajuća okluzija gornjeg dišnog puta tijekom spavanja povezana je s povećanim morbiditetom i mortalitetom od kardiovaskularnih komplikacija. Trenutačno ne postoje informacije o kraniofacijalnim obilježjima osoba s opstruktivnom apnejom u spavanju u Hrvatskoj. Istraživanje je imalo za cilj antropometrijskom i rentgenkefalometrijskom analizom utvrditi kraniofacijalna obilježja pacijenata s opstruktivnom apnejom u spavanju i njihovu povezanost s apnea hipopneja indeksom (AHI). Kod 20 muških ispitanika s OSA i 20 kontrolnih muških ispitanika uzete su antropometrijske mjere i analizirano je 25 varijabli na laterolateralnom rentgenkefalogramu. OSA je definirana kad je AHI 5/h. U usporedbi OSA i kontrolnih ispitanika uočena je statistički značajno povišena srednja vrijednost indeksa tjelesne mase (ITM), opsega vrata (OV) i indeksa glave (IG), a smanjena srednja vrijednost indeksa lica (IL) kod ispitanika s OSA (p <0,01). Ispitanici s OSA su pokazali statistički značajne razlike u rentgenkefalometrijskim varijablama prema kontrolnim ispitanicima: smanjenu duljinu mandibularne ravnine (MP, p<0,05) i prednje kranijalne baze (SN, p <0,01), povećanu udaljenost jezične kosti od mandibularne ravnine (MPH, p<0,05), povećanu duljinu mekog nepca (PNSP, p <0,01), smanjenu širinu gornjeg dišnog puta na dvije razine: velofarinksu (Up-ppw, P-ppw, p <0,01) i orofarinksu (Tbp-ppw, p<0,05; PAS, p<0,01), smanjenu udaljenost jezične kosti od stražnjeg zida farinksa (H-ppw, p<0,01), povećanu kraniocervikalnu angulaciju (OPT-NSL, p <0,01; CTV-NLS, p<0,05), povećan kut između točaka supramentale, menton i jezične kosti (B-Me-H, p<0,05) i povećan kut između točaka spina nasalis posterior, supramentale i jezične kosti (PNS-B-H, p<0,05). Multivarijatna analiza je pokazala vrlo dobru, ali ne i statistički značajnu korelaciju između antropometrijskih prediktorskih varijabli (BMI, IG) i AHI te dobru, ali ne i statistički značajnu korelaciju između rengenkefalometrijskih prediktorskih varijabli (H-ppw, SN i OPT-NSL) i AHI. Ovo istraživanje je pokazalo da između ispitanika s OSA i kontrolnih ispitanika postoje razlike u kraniofacijalnim obilježjima. Rezultati ovog istraživanja ukazuju na potrebu uključivanja specijalista ortodonta u multidisciplinarni tim koji se bavi liječenjem pacijenata s OSA.Introduction: Obstructive Sleep Apnea (OSA) is associated with the excessive drowsiness during the day or with at least two of the following symptoms: sudden awakening with a sensation of suffocation, insufficiently refreshing sleep, tiredness during the day and problems in the cognitive sphere. Repetitive occlusion of the upper airway during sleep is correlated with the increased rates of morbidity and mortality due to cardiovascular complications. Objectives: Currently, there is no data available regarding craniofacial morphology in subjects with obstructive sleep apnea (OSA) in Croatia. The aim of the study was to determine the craniofacial characteristics of subjects with OSA and to assess the correlation of anthropometric and cephalometric variables related to craniofacial morphology with the Apnea Hypopnea Index (AHI). Materials and methods: Anthropometric measurements and upright lateral cephalometric radiographs were obtained from 20 male subjects with OSA and 20 male controls. Twenty five variables were identified and calculated for each cephalometric radiograph. OSA was defined as AHI 5/hour. Results: The OSA subjects showed significantly higher body mass index (BMI), larger neck circumference (NC) and cranial index (CI) and lower facial index (FI) in comparison with the controls (p<0,01). The subjects with OSA showed significant cephalometric features as opposed to the controls: smaller linear distance between gonion and menton (MP, p<0,05) and anterior cranial base (SN, p<0,01), greater linear distance from the hyoid bone to the mandibular plane (MPH, p<0,05), and from the posterior nasal spine to the tip of the soft palate (PNSP, p<0,01). Furthermore, they showed reduced upper airway width at two levels: the velopharynx (Up-ppw, P-ppw, p<0,01), and the oropharings (Tbp-ppw, p<0,05; PAS, p<0,01) and smaller linear distance from the hyoid bone to the posterior wall of the pharynx (H-ppw, p<0,01). They also displayed significantly increased craniocervical angulation (OPT-NSL, p<0,01; CTV-NLS, p<0,05), larger angle between supramentale, menton and hyoid bone (B-Me-H, p<0,05) and larger angle between posterior nasal spine, supramentale and hyoid bone (PNS-B-H, p<0,05). Multivariate analysis showed a very good, but not statistically significant correlation between anthropometric predictor variables (BMI, CI) and AHI, and good, but not statistically significant correlation between cephalometric predictor variables (H-ppw, SN and OPT-NSL) and AHI. Conclusions: This study has proved that OSA subjects and controls have different craniofacial morphology. The results of this study suggest the need to include a specialist orthodontist in the multidisciplinary team dealing with the treatment of OSA patients

The immediate impact of bonded rapid maxillary expansion on the naso-pharyngeal airway patency: a prospective CBCT study

Introduction: Recent studies have utilised cone beam computed tomography (CBCT) for the assessment of the volume of the nasopharyngeal airway space (Guijarro-Martínez and Swennen, 2013, Lenza et al., 2010, Woodside and Linder-Aronson, 1979, Chang et al., 2013). Some of these investigations are based on the analysis of slice data obtained from three dimensional (3D) radiographic images. The usage of a CBCT scan to measure the nasopharyngeal airway volume has drawbacks which include the effect of respiration and tongue position (Abbott et al., 2004), the impact of head posture, lordosis (cranio-cervical inclination) and mandibular morphology on the accuracy of measuring air oro-pharyngeal airways. In addition, published figures to date has not considered the detailed anatomical boundaries of the nasal cavity space, paranasal airway space and other pharyngeal sections collectively (Chang et al., 2013). Aims and objectives: The aim of the study was to assess the validity of the free access software package like ITK Snap in measuring the airways spaces, investigate, using CBCT, the three-dimensional effect of rapid maxillary expansion on the maxillary sinus, the lower part of the nasal cavity, the upper nasopharynx and the upper oropharynx (upper and lower retropalatal spaces), and to correlate the changes in these anatomical spaces with the measured RME appliance split, the dentoalveolar expansion and the gender of the subjects. Materials and methods: This study was carried out on seventeen patients (8 boys, 9 girls; mean age 12.6 + 1.8 years) who required maxillary expansion for the management of narrow upper dental arch. Sample size was calculated using the Researcher’s Toolkit calculator and this indicated that a sample size of 14 patients would produce an Alpha error level or confidence level at 95% and a Beta error level at 20%. Therefore, it was decided to recruit 17 subjects to overcome potential exclusion due to irreproducibility in the head orientation and lordosis. Pretreatment (T1) and immediate post-RME (T2) CBCT images were taken for all the patients. In all CBCT images, head orientation and lordosis were measured using OnDemand 3D software packages. Cases were excluded from the study if the difference in the head orientation and lordosis between the CBCT of T1 and CBCT of T2 was more than 5 degrees. The two scans, T1, T2, were orientated according to a specific protocol and superimposed on the cranial base to standarise the volumteric segemtation and measurements. The impact of RME was assessed by measuring, using ITK snap and OnDemand 3D software packages, the changes in the distance between the intermolar dentoalveolar width at level of molar alveolar crest (IMD), the magnitude of appliance expansion (AE), the volume of respiratory region or the lower part of the nasal cavity (LNC), the volume of the right and left maxillary sinus (RMS and LMS), the volume of the upper nasopharynx (UNP), the subdivisions of the upper oropharynx including the upper and lower retropalatal space (URP and LRP) at T1 and T2. Segmentation of the oro-naso-pharyngeal spaces into multiple segments allows a deailed localisation of the changes and aids in exclusion of any potential masking change of one airway space on adjacent or remote airway space as each segment is associated anatomically and physiologically to different function and/or disorder. The normality of the data was tested using Kolmogorov–Smirnov test. The reproducibility of meaurements was analysed using Paired t-test and interclass correlation coefficient. The volumteric and linear changes was assessed using Student t-test (P&#60;0.05) and Pearson correlation coefficients was used to test the correlation of these changes. Results: Bonded RME has an effective dentoalveolar expansion effect in growing patients (P=0.001) and produced a significant increase in UNP (P=0.045). There was a statistically significant reduction on the URP space (P=0.042), especially in males. There was strong correlation between the increase of the volume of the right and left maxillary sinuses (PCC=0.86) and between appliance expansion and dentolavelar expansion (PCC=0.75). Conclusions: ITK-SNAP software is a reliable package and a single threshold value (-450 grey) is an accurate value. Additionally, this software can be used to measure the size of bony defect in patient with cleft palate before secondary alveolar bone grafting. Bonded RME was an effective dentoalveolar expander in growing patients and the immediate expansion of LNC and UNP might be associated with a reduction in nasal resistance, improvement in the nasal breathing and it can be considered as an option for treatment of Paediatric Obstructive Sleep Apnea Syndrome. Findings of this dtudy showed that there is a sexual dysmorphisim secondary to RME but did not reach the statistical significance. Generally, the effect of the RME on the upper naso-oro-pharyngeal airway spaces followed a mushroom like pattern with the upper parts expanded, the middle part was significantly narrowed while the lower part was mildly, but insignificantly statistically, reduced. However, it is essential to consider that regardless of the benefit of the increase nasal patency of this orthopeadic procedure, it should not done merely for the above purposes solely but only when it is linked to a right indication for RME. A future studies could include a colour mapping for detailed assessment of changes in different part of the oro-naso-pharyngeal space, as the shape changes of the airway space is as important as volumetric changes. Finally, a further randomised clinical trial or comparative study with larger sample size and long term follow up would be beneficial in estimating the real impact of the RME on the airway confirm the findings of this study

Detection and characterisation of genetic associations with canine skull shape and disease

The brachycephalic head conformation is a morphological trait under human selection across many popular breeds such as the Pug. The conformation is characterised by the concurrent rostrocaudal shortening and mediolateral widening of the skull. Overwhelming evidence suggests this skull conformation predisposes breeds to a respiratory morbidity, Brachycephalic Obstructive Airway Syndrome (BOAS) which restricts airflow. This is a major welfare concern. To date, very little is known regarding the genetic factors underpinning canine craniofacial variation or how such factors may influence BOAS aetiology. This project utilised computer tomography scans of 560 dogs to generate high resolution three-dimensional reconstructions of the skull. Geometric morphometric analysis permitted the separation of the confounding influence of size on shape (allometry) at an individual-level – a study design never previously utilised in dogs. Genome-wide association studies (GWAS) using viscerocranial shape changes identified a QTL on chromosome 1 associated with canine brachycephaly. Haplotype mapping refined the critical interval to encompass the SPARC-related modular calcium-binding protein 2 (SMOC2) gene. Leveraging haplotype mapping and whole-genome sequencing, a long interspersed nuclear element (LINE-1) was discovered within intron eight of SMOC2. Transcriptomic analysis revealed the presence of alternative SMOC2 transcripts containing premature stop codons and a downregulation of the gene among brachycephalic carriers of the LINE-1. Models of phenotypic effect predicted that this structural variant explains up to 36% of the total craniofacial variation in the dog. Despite many brachycephalic dogs being fixed for the SMOC2 LINE-1 mutation, heterogeneity in BOAS presentation suggests additional genetic factors contribute to disease risk and presentation. To address this, a respiratory distress syndrome with remarkable similarities to BOAS was assessed in the Norwich Terrier. Endoscopic examinations of 233 Norwich Terriers graded and characterised the respiratory syndrome for the use in a GWAS. A single QTL on chromosome 13 was associated with changes in the structure of the laryngeal saccules and cartilage of affected dogs. The underlying disease-associated haplotype encompassed the disintegrin and metalloproteinase with thrombospondin motifs 3 (ADAMTS3) gene which was observed to harbour a missense mutation in severely affected dogs. Screening for the variant across 89 diverse dog breeds revealed it was enriched in brachycephalic breeds, suggesting that the brachycephalic conformation alone does not completely explain the presentation of BOAS in these breeds. Together, these results provide the opportunity to improve animal welfare by offering genetic screening tests and further our understanding of the condition which is driven by both skeletal and non-skeletal factors

A computational neuromuscular model of the human upper airway with application to the study of obstructive sleep apnoea

Includes bibliographical references.Numerous challenges are faced in investigations aimed at developing a better understanding of the pathophysiology of obstructive sleep apnoea. The anatomy of the tongue and other upper airway tissues, and the ability to model their behaviour, is central to such investigations. In this thesis, details of the construction and development of a three-dimensional finite element model of soft tissues of the human upper airway, as well as a simplified fluid model of the airway, are provided. The anatomical data was obtained from the Visible Human Project, and its underlying micro-histological data describing tongue musculature were also extracted from the same source and incorporated into the model. An overview of the mathematical models used to describe tissue behaviour, both at a macro- and microscopic level, is given. Hyperelastic constitutive models were used to describe the material behaviour, and material incompressibility was accounted for. An active Hill three-element muscle model was used to represent the muscular tissue of the tongue. The neural stimulus for each muscle group to a priori unknown external forces was determined through the use of a genetic algorithm-based neural control model. The fundamental behaviour of the tongue under gravitational and breathing-induced loading is investigated. The response of the various muscles of the tongue to the complex loading developed during breathing is determined, with a particular focus being placed to that of the genioglossus. It is demonstrated that, when a time-dependent loading is applied to the tongue, the neural model is able to control the position of the tongue and produce a physiologically realistic response for the genioglossus. A comparison is then made to the response determined under quasi-static conditions using the pressure distribution extracted from computational fluid-dynamics results. An analytical model describing the time-dependent response of the components of the tongue musculature most active during oral breathing is developed and validated. It is then modified to simulate the activity of the tongue during sleep and under conditions relating to various possible neural and physiological pathologies. The retroglossal movement of the tongue resulting from the pathologies is quantified and their role in the potential to induce airway collapse is discussed

A Textbook of Advanced Oral and Maxillofacial Surgery

The scope of OMF surgery has expanded; encompassing treatment of diseases, disorders, defects and injuries of the head, face, jaws and oral cavity. This internationally-recognized specialty is evolving with advancements in technology and instrumentation. Specialists of this discipline treat patients with impacted teeth, facial pain, misaligned jaws, facial trauma, oral cancer, cysts and tumors; they also perform facial cosmetic surgery and place dental implants. The contents of this volume essentially complements the volume 1; with chapters that cover both basic and advanced concepts on complex topics in oral and maxillofacial surgery

Medical-Data-Models.org:A collection of freely available forms (September 2016)

MDM-Portal (Medical Data-Models) is a meta-data repository for creating, analysing, sharing and reusing medical forms, developed by the Institute of Medical Informatics, University of Muenster in Germany. Electronic forms for documentation of patient data are an integral part within the workflow of physicians. A huge amount of data is collected either through routine documentation forms (EHRs) for electronic health records or as case report forms (CRFs) for clinical trials. This raises major scientific challenges for health care, since different health information systems are not necessarily compatible with each other and thus information exchange of structured data is hampered. Software vendors provide a variety of individual documentation forms according to their standard contracts, which function as isolated applications. Furthermore, free availability of those forms is rarely the case. Currently less than 5 % of medical forms are freely accessible. Based on this lack of transparency harmonization of data models in health care is extremely cumbersome, thus work and know-how of completed clinical trials and routine documentation in hospitals are hard to be re-used. The MDM-Portal serves as an infrastructure for academic (non-commercial) medical research to contribute a solution to this problem. It already contains more than 4,000 system-independent forms (CDISC ODM Format, www.cdisc.org, Operational Data Model) with more than 380,000 dataelements. This enables researchers to view, discuss, download and export forms in most common technical formats such as PDF, CSV, Excel, SQL, SPSS, R, etc. A growing user community will lead to a growing database of medical forms. In this matter, we would like to encourage all medical researchers to register and add forms and discuss existing forms