Centre for Integrated Electronic Systems and Biomedical Engineering (CEBE) Tallinn University of Technology

www.cebe.ttu.ee

Research Results in Biomedical Engineering:

from lab to hospitals

Ivo Fridolin Department of Biomedical Engineering, Technomedicum

Ivo Fridolin

Biofluid Optics

P5

8

Platform based design of embedded systems

Processor architectures

P1

Verification and diagnosis

P2 1

Semicond. technology

P7

5

Testing and reliability

P6

2

4

Applications

Healthcare needs

Other industry

needs

CEBE Competences and Projects Flow

P8

Signal processing methods

Society

Engineering resources,

training

P6 P1 P3 P4 P5

3

P4

6

Brain Studies

P3 7

Cardiovascu-lar diseases

P1

Ivo Fridolin

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Biomedical Engineering Research at TM

R&D Topics:

Brain diagnostics

Diagnostics of cardiovascular diseases

Optical kidney dialysis monitoring

Ivo Fridolin

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Brain Diagnostics: principle and problem

+ The brain bioelectrical activity

(EEG signal) is a good source

of knowledge about the

functioning of the brain

providing objective information

related directly to its ability to

process information.

- Useful diagnostical

information is hidden in

highly complex natural

variability of the EEG signal

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Evaluation of the state of the brain

Detection of characteristic features of electroencphalographyc (EEG) signals related to

i) Mental disorders (depression, stress etc.)

According to the analysis by WHO, depressive disorder is a leading cause of burden

of disease in high- and middle-income countries nowadays and it is projected to take the first place in the world in 2030. Methods for objective and early detection of

depression is an highly actual topic (f.e. the case of Germanwings co-pilot).

ii) Excitation of the brain by external stressor (effect of radiofrequency electromagnetic fields - EMF)

Importance of the problem of the EMF (mobile phones, wifi, relay antenna etc) health effects is underlined in the resolution by European Parliament from 2009 and Council of Europe 2011 on health concerns of population associated with EMF fields and potential danger of EMF. The health protection regulations are still based on the thermal effects only.

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Evaluation of sensitivity of a new method – Spectral Assymmetry Index (SASI)

SASI bases on the balance of powers of two EEG

frequency bands selected higher and lower than

the EEG spectral maximun (alpha band). US8244341B2 granted 14.08.2012: Method and device

for diagnosing a mental disorder by measuring

bioelectromagnetic signals of the brain,”

The classification accuracy of SASI in detection of depression compared to nonlinear EEG

analyses methods, Higuchi’s Fractal Dimension (HFD), Detrended Fluctuation Analysis

(DFA), and Lempel Ziv Complexity (LZC), based on single channel P3 signal

HFD 85 % SASI 85 %

DFA 70,6 % SASI 76,5 %

LZC 77 % SASI 80,5 %

The developed original SASI method provides at least similar sensitivity but much

less computing power compared to traditional nonlinear methods is required.

Bachmann et al., Computational and Mathematical Methods in Medicine, 2013,

Bachmann et al., IFMBE Proceedings 2014

Bachmann et al., IFMBE Proceedings 2015

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FPGA based EEG Analyzer Prototype for implementation of SASI – CEBE project 4

Cooperation between with the Departments of Computer Engineering and Biomedical

Engineering

The project is targeted

to development of

method and device for

early detection of

mental disorders.

The EEG Analyzer is a portable device offering real-time in-field analysis, convenience of

obtaining experimental data for further research and acceleration of the calculation

procedure. It is applicable for evaluation of high-risk personnel such as pilots, police,

military, rescue workers.

The EEG analyser prototype is being under testing in Qvalitas Medical Center, the

largest occupational health care provider in Estonia and has got first positive responses.

Ivo Fridolin

The mechanism of low-level microwave effect on brain

10

Effect on

hydrogen

bonding

Rotation of

dipolar water

molecules

Enhanced

diffusion

Membrane resting

potential of

neurons

Transfer rate of

neurotransmitters

in synapses

Physiological

consequen ces

Parametric excitation of

brain bioelectric

oscillations

Effect on EEG rhythms

First, the nonthermal

mechanism of the

microwave radiation

effect on brain

oscillations was proposed

and proved by

experiments.

Hinrikus et al., Electromagnetic Biology and

Medicine, 2014.

Suhhova et al., Bioelectromagnetics, 2013.

Hinrikus, et al., Int J Radiat Biology, 2011.

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Evaluation of the state of the brain

Cooperation:

North Estonia Medical Center, Estonia

Qvalitas, Estonia

West-Tallinn Central Hospital, Estonia

University of Skopje,

Nalecz Institute of Biocybernetics and Biomedical

Engineering of the Polish Academy of Sciences, Poland

University of Eastern Finland, Finland

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Biomedical Engineering Research at TM

R&D Topics:

Brain diagnostics

Diagnostics of cardiovascular diseases

Optical kidney dialysis monitoring

Ivo Fridolin

Diagnostics of Cardiovascular Diseases

(K.Meigas)

Atherosclerosis is an endovascular inflammatory disease, resulting in a build up of a plaque, which may partially or totally block blood flow in artery.

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Technomedicum

Ivo Fridolin

Diagnostics of Cardiovascular Diseases

(K.Meigas)

Optical methods for early diagnosis of atherosclerosis

Pulse waveform analysis method for estimation of arterial ageing

Novelty – rapid, inexpensive, and noninvasive method

• results are obtained after ~1 minute long registration of optical signal

• Current Standard method: needs trained operator, depends on the subject the registration procedure may take ~15 minutes, expensive equipment

Experimental measurement complex:

Experimental complex for investigation of arterial system using optical, piezoelectrical, phonocardiographical and electrocardiographical methods and signals.

15

Technomedicum

Ivo Fridolin

Diagnostics of cardiovascular diseases

The algoritm for estimation of arterial ageing.

The setup in Centre of Cardiology The setup in DialysisForum

PPGb

PPGd

A

AA

A

PPGAI b

d

Ivo Fridolin

Pulse wave analysis in Technomedicum

Registration of pulse wave from patient for estimation of arterial ageing.

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Ivo Fridolin

TM

Cardiology

team

Interpretation

of biosignals

and signal

processing

algorithms

Project

P3

Optical sensor

Project P1

P3: Development of optical sensor for pulse wave registration from artery

ATI

Design

Team

Design

solutions

Estimation of arterial stiffness based

on pulse wave velocity and pulse

waveform analysis. Pulse waveform

analyzer PA-21 –

device for pulse

waveform analysis

and estimation of

arterial ageing.

New concept:

Novel optical sensor for pulse

wave from arteries and

peripheral blood vessels.

Pulse wave

registration

Ivo Fridolin

Diagnostics of cardiovascular diseases

There is collaboration with North Estonia Medical Center (Tallinn Estonia) in order to carry out studies on diabetes, coronary artery, and chronic kidney disease patients:

Center of General Internal Medicine:

Dr. Anu Ambos

Centre of Nephrology:

Dr. Merike Luman

Center of Cardiology:

Dr. Marika Heinpalu-Kuum

Laboratory:

Dr. Galina Zemtsovskaja

Dr. Marika Pikta

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Biomedical Engineering Research at TM

R&D Topics:

Brain diagnostics

Diagnostics of cardiovascular diseases

Optical kidney dialysis monitoring

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Optical kidney dialysis monitoring

Kidney dialysis -

treatment of the end

stage renal disease

(ESRD) patients by the

artificial kidney (dialysis

machine) in order to

replace all main kidney

functions.

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Clinical kidney dialysis dose

Dialysis dose should be expressed in terms of equilibrated Kt/V

(eKt/V) with the rate equation based on the regional blood flow two-pool

urea kinetic model (evidence level: B).

European Best Practice Guidelines Expert Group on Haemodialysis. Nephrol

Dial Transplant 2002: 17(Suppl 7): S16–S31

4. Minimum adequate dialysis: Guideline 4.1

In anuric patients, treated by three times per week

dialysis, the prescribed target eKt/V should be at least 1.2.

Tattersall, J., A. Martin-Malo, et al. (2007). "EBPG guideline on dialysis

strategies." Nephrology Dialysis Transplantation 22: 5-21.

Current dialysis dose quality parameters are based only on a singel

markermolecule – urea!

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Optical kidney dialysis monitoring

Commercially available options:

• Option Adimea, B. Braun Avitum AG

• Dialysis Dose Monitor, Nikkiso Co, Ltd.

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Dialysis adequacy estimation: what is wrong with Kt/V?

Urea per se is not toxic

There are > 100 uremic retention solutes

removed normally by the kidneys

How removal of a single (non-toxic)

molecule can be valid for all 100 molecules

with different kinetics, i.e. removed differently

during dialysis ?

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Optical kidney dialysis multi component monitoring

MCM:

· Uremic toxins

· Cardiovascular markers

Small

Molecules

< 500 Da

Protein Bound

Molecules

< 500 Da

Middle

Molecules

500 .. 12 000 Da

Enhanced Vision

for

Dialysis Quality

Monitoring

via

Multi component

monitoring

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Multicomponent (MCM©) Sensor concept

Optofluid Technologies OÜ (OFT ) is a spin off company based on the research from CEBE.

MCM© sensor is an official trade mark of OFT.

MCM© sensor

Built-in module

Dialysis

machine

Benefits

• Enhanced dialysis dose quality monitoring

• Cardioprotective therapy assurance

• Improved dialysis care

• Improved life quality

• Longer life expectancy

• Lower healthcare costs

Ivo Fridolin

ATI

Verification

Team

Fault diagnosis

methods

Toolkit

for

dialysis

monitoring

New

algorithms of

signal analysis

Project P2

Optical methods for monitoring of

dialysis

Clinical experiments

Project P5

TM

Biofluids Optics

Team

Cooperation Project P5

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CEBE Cooperation Project P5

The advantages of the SMART algorithm compared to the L-M algorithm are that:

• data processing is done without any time delay providing instantly exact information about the treatment process; • it allows for extrapolating at any time moment the current knowledge about the treatment process to predict the end for the treatment.

Fridolin, I.; Karai, D. ;Kostin, S. ;Ubar, R. (2013). Accurate Dialysis Dose

Evaluation and Extrapolation Algorithms during On-line Optical Dialysis

Monitoring . IEEE Transactions on Biomedical Engineering, 60(5), 1371 - 1377.

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Conclusions: from labs to hospitals