Dynamics of Cardiovascular Ageing

Lead Research Organisation: Lancaster University
Department Name: Physics

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Publications

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BERNJAK A (2012) COHERENCE BETWEEN FLUCTUATIONS IN BLOOD FLOW AND OXYGEN SATURATION in Fluctuation and Noise Letters

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Iatsenko D (2013) Evolution of cardiorespiratory interactions with age. in Philosophical transactions. Series A, Mathematical, physical, and engineering sciences

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Iatsenko D (2015) Nonlinear mode decomposition: a noise-robust, adaptive decomposition method. in Physical review. E, Statistical, nonlinear, and soft matter physics

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Sheppard LW (2012) Testing for time-localized coherence in bivariate data. in Physical review. E, Statistical, nonlinear, and soft matter physics

 
Description We gain wrinkles and lose hair, as we age, but our bodies also change in less obvious but much more important ways. This project studied the age-related alterations that occur in the cardiovascular system - the heart, lungs and network of arteries and veins that carry oxygenated blood and nutrients to every cell of the body and remove the waste products of metabolism. It was already known that the phase of breathing affects the rate at which the heart beats, but that this effect decreases as we age. The research has associated this reduction in heart-lung interaction with changes in the endothelium, the inner lining of all the blood vessels. It involved making non-invasive measurements of blood flow in the skin of 200 healthy subjects of all ages. The analysis focused on very low frequency oscillations in blood flow that can give a measure of the state of the endothelium. The main conclusions are, first, that, to age healthily, you should look after your endothelium and, secondly, that it should be feasible to design an instrument for assessing endothelial health - an endotheliometer.

Our method of measuring the response of the endothelium to an external stimulus enables us to quantify its state of health. We have found -

• A decrease with age in the influence of the lungs on the heart, consistent with earlier work. It means that the cardiovascular system is gradually becoming less well able to function coherently as a single entity.

• That this change can be well-characterised and illustrated by computation of the cardio-respiratory "coupling function" (Figure 1).

• That there is a corresponding decrease with age in the extent to which the endothelium of blood vessels in the skin can react to a chemical stimulus. This reactivity can be taken as a useful measure of the health of the endothelium, and we were able to measure it in-vivo, directly and non-invasively.

• That one can thus define an individual's "endothelial age", which can be either less or more than their chronological age.

• No evidence of coherence between the slow oscillations underlying the heart rate and skin blood flow for frequencies below about 0.1 Hz. This suggests that the lower frequency oscillations, associated with endothelial function, are local in character rather than being under central control for the body as a whole.

• That the endothelium can also be stimulated by a rise in skin temperature, resulting in greatly enhanced low frequency oscillations. Correspondingly, a decrease in skin temperature reduces endothelial activity.

• It will be feasible to create a new medical diagnostic instrument based on a measurement of the endothelial response to temperature changes (patent application submitted). The intention is to design a device that will be the size of a large wrist watch. It will be strapped to the subject's arm for about ten minutes, and will make a series of measurements as the skin is first cooled and then warmed. Its output will be analysed automatically to give a measure of endothelial health. It will thus be easily useable by non-physicists.

As an indicator of general health this endotheliometer has the potential to become almost as widespread in application as the clinical thermometer. We envisage their use by nurses, GPs, and other health professionals, as well as by hospital consultants. Conceivably, in the longer term given the price-reduction associated with mass-production, the endotheliometer could also be purchased by health-conscious members of the public.
Exploitation Route The endotheliometer has the potential become widespread in the health arena but, for this to happen, we will have to take the project to the next stage by construction of a prototype that can be used to attract the interest of medical instrument manufacturers.
Sectors Digital/Communication/Information Technologies (including Software),Healthcare,Other

 
Description Scientifically and technologically the impact is still mostly in the future, and we anticipate that our findings will be used as the basis of new medical instruments: in particular for the assessment of endothelial health through measurement of the reactivity of the microvascular endothelium to changes in temperature. Socially and societally our findings have already resulted in several impacts, including - (a) Impact via talks to the public, schools and other organisations: o Oral presentations about the background and aims of the project were given to Senior Learner's group, Rotary International, Hornby Castle Probus Club, . Spontaneous discussions were also initiated within groups in the local area (students, sports groups, choirs, religious groups). o A Bernjak presented the "21st century thermometer" at Spotlight on Lancaster (29.6. 2011), a workshop for industrialists and commercial users. o A Bernjak presented a poster "Endotheliometer" at the Faculty of Science and Technology Industrial Showcase event, Lancaster University (30.09.2010). o A Stefanovska presented the results Nonlinear dynamics of cardiovascular ageing - A physics approach to physiology of ageing at the Lancaster University Centre for Ageing Research Annual Research Event (30 9 2011). o A Stefanovska spoke to the Kendal Engineering Society (09.02.2012) on The endotheliometer - A thermometer of the 21st century. (b) Impact on a company. Several discussions took place with the company (LEA Medizintechink GmbH, Germany) who make the O2C instrument for simultaneous and continuous measurements of skin blood flow and oxygen saturation. They were sufficiently interested to make adjustments and improvements for targeting researchers. In addition to software upgrades they also developed new probes. c) Impact on NDA Programme This project was part of the NDA programme and we have been involved in several NDA initiatives, discussing findings and implications with other members of the programme and using events such as the "Healthy Ageing Workshop" (22/05/2013) to engage with a range of people from companies, Universities, Local Authorities and the public to showcase this work. d) Impact on clinicians We have discussed the results with clinical colleagues in the cardiovascular field and are developing their awareness of the requirements for a holistic approach to assessing the health of the cardiovascular system and the importance of endothelial health. e) Impact on the mass media The proposed endotheliometer was the subject of a front-page story in the Sunday Times on 11 August 2013, leading to numerous radio and TV interviews.
First Year Of Impact 2011
Sector Healthcare,Other
Impact Types Cultural,Societal

 
Description FST Research Impact Fund
Amount £5,000 (GBP)
Organisation Lancaster University 
Sector Academic/University
Country United Kingdom
Start 08/2016 
End 07/2017
 
Description LU Impact Fund
Amount £6,980 (GBP)
Organisation Lancaster University 
Sector Academic/University
Country United Kingdom
Start 08/2016 
End 07/2017
 
Description Standard research grant: "A device to detect and measure the progression of dementia by quantifying the interactions between neuronal and cardiovascular oscillations"
Amount £594,040 (GBP)
Funding ID EP/M006298/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 05/2015 
End 04/2018
 
Description The physiological significance of cardiorespiratory interactions: bridging between data analysis, mathematical theory and physiological models. Catalyst Seeding
Amount $80,000 (NZD)
Organisation Royal Society of New Zealand 
Sector Learned Society
Country New Zealand
Start 11/2018 
End 11/2020
 
Title Extraction of ridges from 3-D amplitude or power spectra in time-frequency representations of measured signals 
Description The method enables adaptive, universal, extraction of ridge frequencies from time-frequency representations. Being based on dynamic path optimization and fixed point iteration, the method is very fast, and its superior accuracy is also demonstrated. The codes developed are freely available for download. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2016 
Provided To Others? Yes  
Impact The method has been used extensively by other scientists in a variety of different contexts. 
URL https://www.sciencedirect.com/science/article/pii/S0165168416000451
 
Title Nonlinear mode decomposition 
Description This is a numerical method that enables the separation of oscillatory components in complex signals measured either from living systems or more generally. It takes account of nonlinearities. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2015 
Provided To Others? Yes  
Impact There have been citation from scientists working in a diversity of fields. 
URL https://journals.aps.org/pre/abstract/10.1103/PhysRevE.92.032916
 
Title Cardiovascular ageing and hypertension 
Description This dataset available on Pure contains simultaneous recordings of Electrocardiogram (ECG), Respiratory effort (RESP) and right wrist Laser Doppler Flowmetry (LDF) from 29 healthy young (Y, aged 24.4±3.4 years), 22 healthy aged (A, aged 71.1±6.6 years) and 29 treated hypertensive (H, aged 70.3±6.7 years) subjects. All the signals are re-sampled at 40Hz. The duration of the recordings differs between subjects and it is around 30 minutes. 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact The data file is embargoed until 2 May 2018, so no possibility for impact yet. 
 
Title Nonlinear Biomedical Physics database 
Description The database contains data recorded from our previous EU-supported project BRACCIA and ESRC-supported project on "Dynamics of cardiovascular ageing". The BRACCIA data were analysed by members of the group to investigate the effects of general anesthesia with propofol and sevoflurane on cardiovascular and brain dynamics. The data collected during the ESRC-funded project were used to investigate the effect of healthy ageing on cardiovascular dynamics. Both data-sets were also utilized to develop and test new time-series analysis methods. 
Type Of Material Database/Collection of data 
Year Produced 2013 
Provided To Others? Yes  
Impact Subjects before and during general anesthesia were recorded in Lancaster Infirmary and in Oslo National Hospital. A classification analysis based on an optimal set of discriminatory parameters obtained from cardiovascular signals distinguished with 95% success between the awake and anesthetized states. 
URL http://py-biomedical.lancaster.ac.uk/
 
Description Collaboration on hypoxia 
Organisation University of Ljubljana
Department Medical Faculty
Country Slovenia 
Sector Academic/University 
PI Contribution Myself and my group contributed to the study design, the measurement set-up and the analysis of recorded data.
Collaborator Contribution The collaborators, Prof Damjan Osredkar and Prof Tadej Dobevec recruited the subjects, performed the measurements and contributed to the interpretation of results.
Impact A journal paper is drafted and is now being eddied between the co-authors.
Start Year 2017
 
Description Dwain Ekberg 
Organisation Virginia Commonwealth University
Country United States 
Sector Academic/University 
PI Contribution Used our methods to analyze physiological data recorded by Prof Dwain L Eckberg and his collaborators.
Collaborator Contribution Prof Dwain L Eckberg visited Lancaster on several occasions to discuss results of analysis of data he provided, and to prepare joint publications.
Impact 1. Time-frequency methods and voluntary ramped-frequency breathing: a powerful combination for exploration of human neurophysiological mechanisms By: Stankovski, Tomislav; Cooke, William H.; Rudas, Laszlo; et al. JOURNAL OF APPLIED PHYSIOLOGY Volume: 115 Issue: 12 Pages: 1806-1821 Published: DEC 2013 2. Human sympathetic outflows to skin and muscle target organs fluctuate concordantly over a wide range of time-varying frequencies By: Bernjak, Alan; Cui, Jian; Iwase, Satoshi; et al. JOURNAL OF PHYSIOLOGY-LONDON Volume: 590 Issue: 2 Pages: 363-375 Published: JAN 2012
Start Year 2011
 
Description Marcin 
Organisation Medical University of Gdansk
Department Department of Radiology Informatics and Statistics
Country Poland 
Sector Hospitals 
PI Contribution Helped the collaborator to investigate the relationship between blood pressure and pial artery pulsation oscillations in human.
Collaborator Contribution The collaboration comes from a group that has developed a new device for non-invasive measurements of intracranial flow (NIRT). They are contributing signals that when analysed by our methods promise great impact.
Impact Papers in preparation.
Start Year 2015
 
Description Tomislav Stankovski 
Organisation Saints Cyril and Methodius University of Skopje
Country Macedonia, the Former Yugoslav Republic of 
Sector Academic/University 
PI Contribution Aneta Stefanovska and Peter McClintock were PhD and PostDoc supervisors of Dr Tomislav Stankovski. During his stay in Lancaster (2008-2014) Tomislav mastered time series analysis methods and in particular Dynamical Bayesian inference.
Collaborator Contribution Dr Tomislav Stankovski expanded Dynamical Bayesian inference method to include multi-coupling analysis in collaboration with Valentina Ticcinelli, a PhD student funded by Physics Department to work on the project, who coded the algorithm. The method is very relevant for the data recorded during the study.
Impact Dr Tomislav Stankovski co-authored 5 journal papers relevant for our collaborative projects 1. G Nadzinski, M Dobrevski, C Anderson, PVE McClintock, A Stefanovska, M Stankovski, T Stankovski, Experimental Realization of the Coupling Function Secure Communications Protocol and Analysis of Its Noise Robustness, IEEE Transactions on Information Forensics and Security 13 (10), 2591-2601, 2018 2. T Stankovski, T Pereira, PVE McClintock, A Stefanovska, Coupling functions: universal insights into dynamical interaction mechanisms, Reviews of Modern Physics 89 (4), 045001, 2017 3. V Ticcinelli, T Stankovski, D Iatsenko, A Bernjak, AE Bradbury, AR Gallagher, P Clarkson, PVE McClintock, Aneta StefanovskaCoherence and coupling functions reveal microvascular impairment in treated hypertension, Frontiers in physiology 8, 749, 2017 4. T Stankovski, V Ticcinelli, PVE McClintock, A Stefanovska, Neural cross-frequency coupling functions, Frontiers in systems neuroscience 11, 33, 2017 5. T Stankovski, V Ticcinelli, PVE McClintock, A Stefanovska, Coupling functions in networks of oscillators, New Journal of Physics 17 (3), 035002, 2017 and a patent application T Stankovski, A Stefanovska, RJ Young, PVE McClintock, Encoding data using dynamic system coupling, US Patent App. 14/910,547, 2016.
Start Year 2014
 
Title Detecting ASD 
Description The discovery is based on the development of the theory of non-autonomous dynamical systems, methods to analyse time series that contain time-variable dynamics and several related applications where a similar rationale was applied to study e.g. nonlinear dynamics of cardiovascular ageing, or effects of anaesthesia. Our approach takes an explicit account of the intrinsically nonlinear, thermodynamically open, and time-variable nature of the living systems. We considered brain dynamics within this approach and hypothesized that using our methods to analyse EEG data recorded from a control group and children with clinically diagnosed ASD, we can extract bio-markers that are specific to ASD. In the Blackpool hospital, EEGs from 13 ASD (average age 50+-6 months) and 9 control (46+-7 months) males were measured, and 1 min of movement-artefact-free recordings were used in the analyses performed in the Nonlinear and Biomedical Physics Group at Lancaster University. We were able to confirm the hypothesis and extract a set of parameters based on spectral power, phase coherence and coupling functions, that enables a clear distinction between brain dynamics in ASD and control children. 
IP Reference WO 2018/104751 Al 
Protection Patent application published
Year Protection Granted
Licensed No
Impact No additional impact as yet.
 
Title Diagnostic methods and device 
Description The invention relates to a method of diagnosing, or providing a prognosis to, or for providing the likelihood of developing, malignant melanoma in a subject, the method comprising the steps of: (a) measuring two or more markers in blood perfusion dynamics at and/or around a skin lesion site; and (b) determining if the two or more markers is different to a normal value. The invention also relates to a device for diagnosing/providing a prognosis to/for malignant melanoma in a subject. 
IP Reference Patent number: 9907507 
Protection Patent granted
Year Protection Granted 2018
Licensed No
Impact Not yet.
 
Title MODA 
Description MODA is a toolbox that provides a set of methods to deal with signals affected by time variability. Currently, it contains 5 methods, including wavlet analysis, wavelet-based phase coherence analysis, wavelet-based bispectral analysis, ridge-extraction and coupling function analysis. It is intended to be very user friendly to be used by the wider scientific community. 
Type Of Technology Software 
Year Produced 2018 
Impact Too early. 
 
Title Nonlinear Biomedical Physics toolboxes 
Description Currently, it includes the following toolboxes: 1. Wavelet Phase Coherence, 2. TACTS Matlab toolbox, 3. TEDBI_Bayesian_Toolbox, 4. Time_Frequency_Representations and 5. Nonlinear_Mode_Decomposition 
Type Of Technology Software 
Year Produced 2013 
Open Source License? Yes  
Impact To date a total of 445 registered downloads. 
URL http://py-biomedical.lancaster.ac.uk/
 
Description Biological Oscillations conference 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Stefanovska and her group organised the 9th conference of the European Study Group on Cardiovascular Oscillations which took place in Lancaster from 10th to 14th April 2016. This was also the first International Conference on Biological Oscillations.
The aim of the conference was to provide an interdisciplinary forum for discussions of biological oscillations between researchers drawn from areas such as physics, mathematics, engineering, computer science, cardiovascular regulation, neuroscience, time-series analysis, theory of nonlinear oscillatory dynamics, information processing, cardiovascular and microvascular physiology, cell biology and clinical sciences.
In addition to the signal processing view of cardiovascular oscillations this conference expanded to incorporate a more physics-based approach. It also generalized the topic to include all biological oscillations.
Year(s) Of Engagement Activity 2016
URL http://www.physics.lancs.ac.uk/ESGCO2016/
 
Description Contribution to Headstart Programme 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact 30 Y12 Physics students from across the UK participated in the Headstart course. All students are studying A level Physics and another science in many cases and Mathematics and are high ability as indicated by their teachers. Our group organised a whole day event for the students and provided three workshop sessions: Physics of the Brain, Physics of the Cardiovascular System and Physics of the Cell. After a few introductory talks by members of the group students did either measurements or simulations, analysed their data and then presented the results to their audience.
Year(s) Of Engagement Activity 2017
URL http://www.etrust.org.uk/headstart/whatisheadstart
 
Description Contribution to Hgher Education Day at Runshaw College 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Talk stimulated plenty of questions!

Nothing notable evident to date.
Year(s) Of Engagement Activity 2015
 
Description Data Science Institute workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Data Science Institute organized a Streaming Data workshop that was held in the Low Wood hotel 18-19 July 2016. I presented our work and participated in many activities of the workshop.The workshop was used to

• explore current Streaming Data research activities at Lancaster;
• identify challenges which can draw mutual interest;
• and develop ideas for future research and funding opportunities in this area.
Year(s) Of Engagement Activity 2016
 
Description Healthy Ageing and Older People 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact The event was in the Council House in Birmingham on the 22 May 2013 under the aegis of the New Dynamics of Ageing programme. It was intended to bring the results of research by several groups to the attention of carers and the general public. We made a brief presentation, showed a poster with main findings of our project and engaged in extensive discussion.
Year(s) Of Engagement Activity 2013
 
Description Physics Department Colloquium, Royal Holloway, University of London, 18 May, 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Delivered a talk "Understanding systems operating far from equilibrium from the perspective of time-varying dynamics" and enjoyed vigorous discussion about differences in living and non-living systems dynamics.
Year(s) Of Engagement Activity 2018
 
Description Physics Master Class: Waves and Oscillations featuring Biomedical Physics Research 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact 12 A-level students attended a whole day event which consisted of an introductory talk, two biomedical research taster projects and an oscillations and waves lab to complement their A-level studies. Students prepared group presentations and presented the results of their work. Several feedback - both from students and their A-level teachers indicate that students greatly enjoyed the day and developed an interest in the field.
Year(s) Of Engagement Activity 2017
 
Description School visit to Bolton Muslim Girls' School 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Our talk sparked lively and spirited discussions with both pupils and teachers.

N/A
Year(s) Of Engagement Activity 2013
 
Description Seminar (Reading) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact Talk at the School of Biological Sciences Research Seminar Series, University of Reading, 16 October, 2018 to students of Biomedical Sciences and Biomedical Engineering and their lecturers interested in the filed of Biological Oscillators. Discussed examples related to ageing, dementia, ASD and the cell, cardiovascular system and brain oscillatory dynamics.
Year(s) Of Engagement Activity 2018
URL https://www.reading.ac.uk/biologicalsciences/SchoolofBiologicalSciences/Research/sbs-research-semina...
 
Description Talk to Nelson and Colne Sixth Form College 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Gave the talk twice to different audiences who were highly reactive and asked numerous questions.

N/A
Year(s) Of Engagement Activity 2014
 
Description The NDA Programme & Age UK Research Showcase of the Decade 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact The event was jointly organised by the New Dynamics of Ageing Programme and Age UK at the Business Design Center in London on 21 October 2013, and attracted several hundred participants including policymakers, politicians, media, experts and the public. In the Session 1 - From Cell to Society, New dynamics in understanding the ageing process towards
extending healthspan Aneta Stefanovska made presentation entitled Cardiovascular ageing.
Year(s) Of Engagement Activity 2013
URL http://www.newdynamics.group.shef.ac.uk/showcase.html