Towards Wearable Continuous Point-of-Care Monitoring for Deep Vein Thrombosis of the Lower Limb, EMBEC 2024

Kaldoudi E, Marozas M, Jurkonis R, Pousset N, Legros M, Kircher M, Novikov D, Sakalauskas A, Moustakidis P, Ayinde B, Moltani LA, Balling S, Vehkaoja A, Oksala N, Macas A, Balciuniene N, Bigaki M, Potoupnis M, Papadopoulou S-L, Grandone E, Gautier M, Bouda S, Schloetelburg C, Prinz T, Dionisio P, Anagnostopoulos S, Drougka I, Folkvord F, Drosatos G, Didaskalou S and the ThrombUS+ Consortium, Towards Wearable Continuous Point-of-Care Monitoring for Deep Vein Thrombosis of the Lower Limb. In: Jarm, T., Šmerc, R., Mahnič-Kalamiza, S. (eds) 9th European Medical and Biological Engineering Conference. EMBEC 2024. IFMBE Proceedings, vol 113. Springer, Cham. https://doi.org/10.1007/978-3-031-61628-0_36

Presented by Dr. Stelios Didaskalou, ThrombUS+ Project Manager

1. Presented by
S. Didaskalou,
ThrombUS+ Project Manager, ATHENA RC
12 June 2024
Co-funded by the
European Union
Towards Wearable Continuous Point-of-Care Monitoring for Deep Vein
Thrombosis of the Lower Limb
E. Kaldoudi, S. Didaskalou and the ThrombUS+ Consortium

2. EMBEC 2024| Portorož, Slovenia | 12 June 2024
2
Deep Vein Thrombosis (DVT) is the
clotting of blood in a deep vein of
the pelvis or an extremity
(usually calf or thigh)
https://www.usaveinclinics.com/vein-disease/deep-vein-thrombosis-dvt/ June 2024
https://www.cdc.gov/blood-clots/data-research/facts-
stats/index.html#:~:text=The%20precise%20number%20of%20people,die%20of%20VTE%20each%20year . June 2024
a clot is mainly composed of fibrin and red
blood cells and may contain platelets,
leukocytes and other compounds
a clot usually forms around the valves
in the deep veins of the leg
a clot forms in a matter of seconds or
minutes depending on the individual
when present, the clot disturbs the flow of
blood and results in pain and swelling
the clot might be pushed via the heart to
the lungs where it can block an artery,
what is know as pulmonary embolism,
an acute, life-threatening event

3. EMBEC 2024| Portorož, Slovenia | 12 June 2024
3
Deep Vein Thrombosis (DVT) is a major preventable cause
of morbidity and mortality worldwide
▪3
rd
most frequent vascular diagnosis after heart attack and stroke,
▪affects more than 1,000,000 Americans per year
affects more than 700,000 Europeans per year
▪1/2 of people with DVT
experience a sudden pulmonary embolism
▪about 1/4 of those who have a pulmonary embolism die from it
▪1/3 to 1/2 of people who have a DVT episode will have long-term
complications caused by the damage the clot does to the valves in the vein
▪annual health expenditure related to DVT is €8.5 billion in EU
Olaf Met al. Deep Venous
Thrombosis. EmergMed Clin North
Am. 2017 doi:
10.1016/j.emc.2017.06.003
Cohen AT et al. ThrombHaemost.
2007 Oct;98(4):756-64
Barco S et al.ThrombHaemost. 2016
Apr;115(4):800-8. doi: 10.1160/TH15-
08-0670

4. EMBEC 2024| Portorož, Slovenia | 12 June 2024
currently, ultrasonography is the
method of choice for DVT diagnosis
4
▪direct visualization of the thrombus
▪Doppler to assess venous flow
▪compression ultrasound
when DVT is present,
vein does NOT fully collapse
artery
vein
compression US
>90% sensitive >95% specific

5. EMBEC 2024| Portorož, Slovenia | 12 June 2024
other modalities for DVT diagnosis
5
Light Reflection Rheography
measures blood volume changes in
peripheral veins via reflection of light
Electrical Impedance Plethysmography
measures blood volume changes in
peripheral veins via electrical impedance
Credits: S. Balling, medis.

6. EMBEC 2024| Portorož, Slovenia | 12 June 2024
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prompt diagnosis of DVT is crucial!
patients are referred for an ultrasound
when they present DVT-related clinical
symptoms
however,…
up to 2/3 of DVT episodes are clinically
silent and patients are symptom free
pulmonary embolism events are
acute, and 1/4 of these result in death
immediately or in a few hours, before
a treatment can be applied

7. EMBEC 2024| Portorož, Slovenia | 12 June 2024
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Wearable Continuous, Point-of-Care
Monitoring, Risk Estimation and Prevention
for Deep Vein Thrombosis
Horizon Innovation Action | No. 101137227
Co-funded by the European Union
Academia
Research
institute
Hospitals
Social
science
experts
Regulatory
experts
Clinical
trial
experts
Industry
Duration: 42 months
Start: 1 January 2024
End: 30 June 2027
Budget: 9.5 M€
18 partners
from 8 countries
Greece, Lithuania, France, Germany, USA, Finland, Italy, Spain

8. EMBEC 2024| Portorož, Slovenia | 12 June 2024
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wearable ultrasound for DVT continuous monitoring
coupled with
electrical impedance plethysmography
light reflection rheography
activity sensors (patient and doctor empowerment)
other info (assessment of DVT risk)
with AI support for autonomous monitoring,
DVT risk assessment and
DVT early detection image generated by MS Designer https://designer.microsoft.com/image-creator
prompt: “a patient lying in a bed with subtle multiple sensors on the leg embedded
in a legging with a screen in the background displaying leg movements”

9. EMBEC 2024| Portorož, Slovenia | 12 June 2024
9A
B A B
2 types of bulk technology US
transducers by VERMON
MEMS technology US
transducer by FRAUNHOFER
Beamforming by
TELEMED
smart textile
wearable by
ComfTech
electrical impedance
plethysmography
by TAU
light reflection
rheography
by MEDIS
activity sensor
network
by KTU
pressure
micropump
by KTU
AI based ultrasound
DVT detection by
EchoNous
AI based DVT
detection based on
EIP and LRR
by TAU and MEDIS
DVT risk detection, activity
based serious game and
extended reality by
ATHENA
central
intelligence
and app
by ATHENA

10. EMBEC 2024| Portorož, Slovenia | 12 June 2024
10
Clinical Studies
AConventional ultrasound image set collection to create a training data set
Participants >3000
B1Training data set collection using the prototype wearable ultrasound to fine tune the AI
model
Participants >500
B2Physiological signals, lower limb activity and plethysmography measurements via the
ThrombUS+ prototype wearable sensor components from healthy volunteers
Participants >60
C1Early feasibility study of the ThrombUS+ integrated prototype in patients in the
postoperative ward
Participants 25-50
C2Prospective, double-blinded, pilot study evaluating artificial intelligence driven automatic
detection of deep vein thrombosis by the ThrombUS+ device compared to standard
ultrasound imaging in patients suspected for deep vein thrombosis
Participants: 50-100

11. EMBEC 2024| Portorož, Slovenia | 12 June 2024
patient centric design
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•clinical survey amongst experts to
identify major patient categories in risk
of DVT and in need of continuous
monitoring
•expert structured interviews to identify
patient practical needs, opportunities
and barriers for continuous monitoring
•patient focus groups (planned)
7 major reference use cases
Credits: Lucas J. Segal and Federico Puppo, PBY
ThrombUS+
Reference Use Cases
after surgery (neurosurgery,
lower-body orthopedic,
cardiovascular)
perinatal care
cancer
obesity
autoimmune diseases &
genetic disorders
based on literature, of all DVT episodes
50% no obvious cause
20% cancer related
20% after surgery

12. EMBEC 2024| Portorož, Slovenia | 12 June 2024
data driven approach
12Table 1. Hospitals participating in the ThrombUS+ Clinical Study A.
Hospital TAU LSMU GNP CSS-IRCCS HSV Total
Country Finland Lithuania Greece Italy France 5 countries
Number of beds 1,000 2,232 745 750 976 5,703
Hospitalizations per year 82,897 83,192 94,205 45,000 30,078 335,372
Out-patients per year 1,162,227 1,228,783 244,227 300,000 236,164 3,171,401
Patients scanned for suspected
DVT per year
3,500 4,000 939 2,400 350 11,189
Table 1. Collective numerical data for the ThrombUS_A study.
Total number of patients referred for an ultrasound scan for suspected DVT per year 11,189
Positive DVT scans per year 2,547
Positive DVT scans as a percentage of referred and scanned patients per year 22%
Duration of the study (in months) 12
Estimated patients available for recruitment 11,000
Expected patients to recruit 3,000
Expected patients to recruit as a percentage for available for recruitment 27%
Expected positive scans in the recruited population (20%) 660

conventional ultrasound image set
collection to create a training data set
Participants >3000
Drougka I, Clinical studies initiation package - Study A, Deliverable 7.1, ThrombUS+ Horizon Europe Innovation
Action, EC Grant Agreement No. 101137227, 31 May 2024, https://doi.org/10.5281/zenodo.11371924
the annotated data set will
be available to the public!Table 1. A summary of milestones regarding the ThrombUS+ Clinical Study A
Milestone Planned date
IRB/IEC approval June 2024
Start of data collection July 2024
Midterm recruitment report December 2024
End of data collection June 2025
Final report of study results July 2025

13. EMBEC 2024| Portorož, Slovenia | 12 June 2024
compliance by design
13
research based on a regulatory
compliance monitoring plan
creation of regulatory templates
for the technical documentation
preparation of draft documents
from templates
distribution of draft documents
to project partners for feedback
review of feedback and
incorporation into draft documents
knowledge transfer on
specific regulatory topics
Credits: Thorsten Prinz, VDE

14. EMBEC 2024| Portorož, Slovenia | 12 June 2024
Regulations
•Regulation (EU) 2017/745 on medical devices (MDR)
•Implementing Regulation (EU) 2021/2226 on rules of implementing MDR
•Regulation (EU) 2016/679 General Data Protection Regulation (GDPR)
•Regulation (EU) 2024/… on Artificial Intelligence Act (AIA)
•Regulation (EU) No 536/2014 on Clinical Trials
Guidelines
•MDCG in applying MDR
•Guidelines of Notified Bodies
•Guideline for good clinical practice E6(R2),
EMA/CHMP/ICH/135/1995 Committee for Human Medicinal Products
•World Medical Association Declaration of Helsinki, 1964
14

15. EMBEC 2024| Portorož, Slovenia | 12 June 2024
open science
Standards
•DICOM
Digital Imaging and Communication in Medicine
•ICD
International Classification of Diseases
•SNOMED-CT
Systemized Nomenclature of Medicine – Clinical Terms
15
https://thrombus.eu/
https://zenodo.org/communities/thrombus/

17. Cite as:
Kaldoudi E, Marozas M, Jurkonis R, Pousset N, Legros M,
Kircher M, Novikov D, Sakalauskas A, Moustakidis P,
Ayinde B, Moltani LA, Balling S, Vehkaoja A, Oksala N,
Macas A, Balciuniene N, Bigaki M, Potoupnis M,
Papadopoulou S-L, Grandone E, Gautier M, Bouda S,
Schloetelburg C, Prinz T, Dionisio P, Anagnostopoulos S,
Drougka I, Folkvord F, Drosatos G, Didaskalou S and the
ThrombUS+ Consortium, Towards Wearable Continuous
Point-of-Care Monitoring for Deep Vein Thrombosis of the
Lower Limb. In: Jarm, T., Šmerc, R., Mahnič-Kalamiza, S.
(eds) 9th European Medical and Biological Engineering
Conference. EMBEC 2024. IFMBE Proceedings, vol 113.
Springer, Cham. https://doi.org/10.1007/978-3-031-61628-
0_36
Views and opinions expressed are however those of the
author(s) only and do not necessarily reflect those of the
European Union or the granting authority HADEA.
Neither the European Union nor the granting authority
can be held responsible for them.
https://www.linkedin.com/co
mpany/thrombus-eu-project/
https://thrombus.eu/
[email protected]
Co-funded by the
European Union
Contact:
Prof. Eleni Kaldoudi
Coordinator
[email protected]
Dr. Stelios Didaskalou
Project Manager:
[email protected]