ThrombUS+ Project Presentation - June 2024

Kaldoudi E., ThrombUS+ Project Overview, Horizon Europe Health Cluster Networking Meeting, Online Event, 26 June 2024

1. Project Overview
E. Kaldoudi |ATHENA RC | Greece
Horizon Europe Health Cluster Networking Meeting
26 June 2024
Co-funded by the
European Union

2. Co-funded by the European UnionHorizon Europe Health Cluster Networking Meeting | 26 June 2024
Wearable Continuous Point-of-Care Monitoring,
Risk Estimation and Prevention for Deep Vein Thrombosis
Project type: IA (Innovation Action)
Project Budget: 9,565,763.75 €
EU funding: 8,141,251.25 €
Duration: 42 months
Start: 1 January 2024
End: 30 June 2027
Invited: 04 August 2023
Signed: 08 December 2023
Call Identifier: HORIZON-HLTH-2023-TOOL-05-05
Call title: Harnessing the potential of real-time data
analysis and secure Point-of-Care computing for the
benefit of person-centred health and care delivery
Program: Horizon Europe, 4. Health, 2023-2024
Destination: 5. Unlocking the full potential of new tools,
technologies and digital solutions for a healthy society
Proposal submitted: 13 April 2023
2

3. Co-funded by the European Union
Greece
Lithuania
Germany
Italy
France
Finland
Spain
USA
Horizon Europe Health Cluster Networking Meeting | 26 June 2024 3

4. research industry
hospitals

5. Co-funded by the European Union
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
Horizon Europe Health Cluster Networking Meeting | 26 June 2024 5

6. Co-funded by the European Union
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 25% 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
Horizon Europe Health Cluster Networking Meeting | 26 June 2024 6

7. Co-funded by the European UnionHorizon Europe Health Cluster Networking Meeting | 26 June 2024
clinical conditions most closely
associated with DVT
surgery or trauma
malignancy
prolonged immobility
pregnancy
congestive heart failure
varicose veins
obesity
advancing age
history of DVT
of all DVT episodes
50% no obvious cause
20% cancer related
20% after surgery
7

8. Co-funded by the European Union
graduated
compression stockings
Horizon Europe Health Cluster Networking Meeting | 26 June 2024
Sachdeva A, Dalton M, Lees T. Graduated compression stockings for prevention of deep vein
thrombosis. Cochrane Database Syst Rev. 2018 Nov 3;11(11):CD001484.
https://doi.org/10.1002/14651858.CD001484.pub4
Yang SD, Ning SH, Zhang LH, Zhang YZ, Ding WY, Yang DL. The effect of lower limb rehabilitation
gymnastics on postoperative rehabilitation in elderly patients with femoral shaft fracture: A
retrospective case-control study. Medicine (Baltimore). 2016 Aug;95(33):e4548.
https://doi.org/10.1097/MD.0000000000004548.
rehabilitation gymnastics
prevention of deep vein thrombosis employs
anti-thrombotic medication and …
8

9. Co-funded by the European Union
currently, ultrasonography is the
method of choice for DVT diagnosis
▪direct visualization of the thrombus
▪Doppler to assess venous flow
▪compression
ultrasound
while compressing with the US probe
till the artery starts to compress,
when normal,
the vein fully collapses
when DVT is present,
vein does NOT collapse
artery
vein
compression US
Horizon Europe Health Cluster Networking Meeting | 26 June 2024 9

10. Co-funded by the European Union
other modalities for DVT diagnosis
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
changes
Credits: S. Balling, medis.
Horizon Europe Health Cluster Networking Meeting | 26 June 2024 10

11. Co-funded by the European Union
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 about 25% of these result in
death immediately or in a few hours,
before a treatment can be applied
Horizon Europe Health Cluster Networking Meeting | 26 June 2024 11

12. Co-funded by the European Union
wearable ultrasound for DVT continuous monitoring
coupled with
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”
Horizon Europe Health Cluster Networking Meeting | 26 June 2024 12

13. Co-funded by the European UnionHorizon Europe Health Cluster Networking Meeting | 26 June 2024A
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
WP3
WP4
WP5
WP3
WP6
13

14. Co-funded by the European UnionHorizon Europe Health Cluster Networking Meeting | 26 June 2024
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
14

15. Co-funded by the European UnionHorizon Europe Health Cluster Networking Meeting | 26 June 2024
Hospital Name Total TAU LSMU GNP CSS- IRCCS HSV
Country 5 countries Finland LithuaniaGreece Italy France
Number of beds 5,703 1,000 2,232 745 750 976
Hospitalizations per
year
335,372 82,897 83,192 94,205 45,000 30,078
Out-patients per year3,171,401 1,162,227 1,228,783244,227 300,000 236,164
Patients scanned for
suspected DVT per
year
11,189 3,500 4,000 939 2,400 350
Positive scans for DVT
per year
2,255 700 800 188 500 67
Surgical operations per
year
136,252 40,896 66,254 10,669 8,000 10,433
Orthopaedics
operations per year
21,232 13,000 4,945 1,137 600 1,550
*based on data for year 2022
15

16. Co-funded by the European Union
patient centric design
•clinical survey amongst experts to
identify major patient categories in risk
of DVT and in need of continuousaaa
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
perinatal care
cancer
obesity
prolonged immobility
history of thrombosis
genetic disorders
based on literature, of all DVT episodes
50% no obvious cause
20% cancer related
20% after surgery
Horizon Europe Health Cluster Networking Meeting | 26 June 2024 16

17. Co-funded by the European Union
data driven approach Table 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
the annonated data set will
be available to the public!
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 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

Horizon Europe Health Cluster Networking Meeting | 26 June 2024 17

18. Co-funded by the European Union
compliance by design
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
Horizon Europe Health Cluster Networking Meeting | 26 June 2024 18

19. Co-funded by the European Union
open science
Standards
•DICOM
Digital Imaging and Communication in Medicine
•GDF
Geographic Data Files
•ICD
International Classification of Diseases
•SNOMED-CT
Systemized Nomenclature of Medicine – Clinical Terms
https://thrombus.eu/
https://zenodo.org/communities/thrombus/
Horizon Europe Health Cluster Networking Meeting | 26 June 2024 19

20. Co-funded by the European Union
work
package
breakdown
WP 1. Management
WP 2. Requirements and product co-design
WP 3. Ultrasound sensing
WP 4. Plethysmography, activity sensors and wearable
WP 5. Decision support and action intelligence
WP 6. Integration and validation
WP 7. Clinical studies
WP 8.Dissemination & Communication
WP 9.Exploitation, and Commercialization
Horizon Europe Health Cluster Networking Meeting | 26 June 2024 20

21. WP10. Exploitation & Commercialization
Study A – Conventional
data collection
Τ7.2
Automated US DVT
detection
Τ5.1
Clinical studies
initiation
Τ7.1
ThrombUS+ specsΤ6.1
Hardware
integration
Τ6.3
Software integration
intelligence and app
Τ6.4
Testing methodology
and plans
Τ6.2
Patient-centric cases and
requirements definition
Τ2.1
Regulatory framework,
security, safety and ethics
Τ2.2
WP1. Management
WP8. Dissemination & Communication
WP9. Exploitation & Commercialization
Testing, signal quality and
performance enhancements
Τ4.5
Manufacturing of
wearable prototypes
Τ4.6
Wearable development and
integration with sensors
Τ4.4
Testing, image quality and
performance enhancements
Τ3.5
Manufacturing of
US prototypes
Τ3.6
Transducer/cuff control and
image formation
Τ3.4
Studies B – Data collection
by prototype components
Τ7.3
Studies C – Clinical
trials
Τ7.4
Hardware and
software integration
& communications
Τ6.5
Posting of clinical
trial results
Τ7.5
Technical and functional
requirements
Τ2.4
Co-creation of wearable
strap and sock design
Τ2.3
Light reflection rheography
sensors development
Τ4.2
Lower limb activity sensor
network development
Τ4.3
Impedance sensors
development
Τ4.1
Precise tissue compression
actuator
Τ3.3
Ultrasound transducer array
Bulk technology
Τ3.1
Ultrasound transducer array
MEMS technology
Τ3.2
DVT risk estimation Τ5.3
Automated
plethysmography
DVT detection
Τ5.2
Serious game for
DVT prevention
Τ5.5
Extended reality for
guidance
Τ5.4
Horizon Europe Health Cluster Networking Meeting | 26 June 2024 21

22. Co-funded by the European UnionHorizon Europe Health Cluster Networking Meeting | 26 June 2024
# No Lead Type DissemMonth Date
1 D8.1 SciGen DEC PU 1Jan 2024
2 D1.1 ATHENA DEC SEN 1Jan 2024
3 D10.1 ATHENA ETHICS SEN 1Jan 2024
4 D1.2 ATHENA R SEN 3Mar 2024
5 D1.3 MEDEA R SEN 3Mar 2024
6 D8.2 SciGen R PU 3Mar 2024
7 D9.1 VDE R PU 3Mar 2024
8 D1.4 ATHENA DMP PU 4Apr 2024
9 D7.1 PHAZE R PU 5May 2024
10 D2.1 PBY R PU 6Jun 2024
11 D2.2 VDE R PU 8Aug 2024
12 D2.3 KTU R PU 10Oct 2024
13 D2.4ComfTech R SEN 12Dec 2024
14 D3.1 VERMON DEM SEN 12Dec 2024
15 D3.2FRAUNHOFER DEM SEN 12Dec 2024
16 D3.3 KTU DEM SEN 12Dec 2024
17 D4.1 TAU DEM SEN 12Dec 2024
18 D4.2 MEDIS DEM SEN 12Dec 2024
19 D4.3 KTU DEM SEN 12Dec 2024
20 D7.2 PHAZE R PU 12Dec 2024
21 D7.3 PHAZE R PU 13Jan 2025
22 D6.1 KTU R PU 14Feb 2025
23 D3.4 TELEMED DEM SEN 15Mar 2025
24 D7.4 PHAZE R PU 15Mar 2025
25 D4.4ComfTech DEM SEN 16Apr 2025
26 D6.2 KTU R PU 18Jun 2025
27 D3.5 KTU R PU 19Jul 2025
28 D4.5 KTU R PU 19Jul 2025
# No Lead Type DissemMonth Date
29 D7.5 PHAZE R PU 20Aug 2025
30 D3.6 TELEMED DEM SEN 21Sep 2025
31 D4.6ComfTech DEM SEN 21Sep 2025
32 D1.5 ATHENA DMP PU 24Dec 2025
33 D7.6 PHAZE R PU 24Dec 2024
34 D6.3 KTU DEM SEN 26Feb 2026
35 D8.3 ATHENA DATA PU 26Feb 2026
36 D5.1EchoNous DEM SEN 28Apr 2026
37 D5.2 TAU DEM SEN 28Apr 2026
38 D5.3 ATHENA DEM SEN 28Apr 2026
39 D5.4 ATHENA DEM SEN 28Apr 2026
40 D5.5 ATHENA DEM SEN 28Apr 2026
41 D6.4 ATHENA DEM SEN 28Apr 2026
42 D7.7 PHAZE R PU 29May 2026
43 D6.5 KTU DEM SEN 32Aug 2026
44 D7.8 PHAZE R PU 36Dec 2026
45 D1.6 ATHENA R SEN 42Jun 2027
46 D1.7 MEDEA R SEN 42Jun 2027
47 D7.9 PHAZE R PU 42Jun 2027
48 D8.4 SciGen R PU 42Jun 2027
49 D8.5 SciGen R PU 42Jun 2027
50 D9.2 VDE R PU 42Jun 2027
51 D9.3 PBY R PU 42Jun 2027
52 D9.4 MEDEA R SEN 42Jun 2027
53D10.5 ATHENA ETHICS SEN 42Jun 2027
54D10.2 ATHENA ETHICS SEN 12Dec 2024
55D10.3 ATHENA ETHICS SEN 24Dec 2025
56D10.4 ATHENA ETHICS SEN 36Dec 2026
52 +4
deliverables
22

23. Co-funded by the European Union
project progress
•1
st
milestone
reached
•9 deliverables
submitted on time
Horizon Europe Health Cluster Networking Meeting | 26 June 2024 23

24. Project Meeting 02 |Kaunas, Lithuania | 14-15 May 2024
Seal of Excellence by France
the project scored the maximum of 4/4
in all 10 evaluation criteria

25. Co-funded by the European Union
submitted public deliverables or publishable summaries
can be viewed in the project website and
in the project’s community in Zenodo
Horizon Europe Health Cluster Networking Meeting | 26 June 2024
https://thrombus.eu/
25

26. Alexandroupoli, Jan 2024
Kaunas, May 2024 Kaunas, May 2024
Kaunas, May 2024
Kaunas, May 2024
Kaunas, May 2024

27. Coordinator: Prof. Eleni Kaldoudi, Coordinator
[email protected]
Project Manager: Dr. Stelios Didaskalou
[email protected]
https://www.linkedin.com/co
mpany/thrombus-eu-project/
https://thrombus.eu/
[email protected]
Co-funded by the
European Union